Dynamic Contrast-enhanced CT Lymphangiography to Quantify Thoracic Duct Lymphatic Flow.

Background CT lymphangiography has been used to image the lymphatic anatomy and assess lymphatic abnormalities. There is, however, a need to develop a method for quantification of lymphatic flow rate in the thoracic duct (TD). Purpose To develop and validate a TD lymphatic flow measurement technique using dynamic contrast-enhanced CT lymphangiography. Materials and Methods Lymphatic flow rate was measured with two techniques: a first-pass analysis technique based on a single compartment model and a thresholding technique distinguishing between opacified and nonopacified voxels within the TD. The measurements were validated in a swine animal model between November 2021 and September 2022. CT images were acquired at 100 kV and 200 mA using a fast-pitched helical scan mode covering the entire TD following contrast material injection into the bilateral inguinal lymph nodes. Two helical CT scans, acquired at the base and peak contrast enhancement of the TD, were used to measure lymphatic flow rate. A US flow probe surgically placed around the TD provided the reference standard measurement. CT lymphatic flow measurements were compared with the reference US flow probe measurements using regression and Bland-Altman analysis. Repeatability was determined using repeated flow measurements within approximately 10 minutes of each other. Results Eleven swine (10 male; mean weight, 43.6 kg ± 2.6 [SD]) were evaluated with 71 dynamic CT acquisitions. The lymphatic flow rates measured using the first-pass analysis and thresholding techniques were highly correlated with the reference US flow probe measurements (r = 0.99 and 0.91, respectively) and showed good agreement with the reference standard, with Bland-Altman analysis showing small mean differences of 0.04 and 0.05 mL/min, respectively. The first-pass analysis and thresholding techniques also showed good agreement for repeated flow measurements (r = 0.94 and 0.90, respectively), with small mean differences of 0.09 and 0.03 mL/min, respectively. Conclusion The first-pass analysis and thresholding techniques could be used to accurately and noninvasively quantify TD lymphatic flow using dynamic contrast-enhanced CT lymphangiography. © RSNA, 2023 See also the editorial by Choyke in this issue.

Endovascular Treatment of Renal Artery Thrombosis in Living-Donor Kidney Transplant Recipient With Severe COVID-19 Disease.

PURPOSE: Coronavirus disease 2019 (COVID-19) patients have a higher prevalence of micro-and macrovascular thrombotic events. However, the underlying mechanism for the increased thrombotic risk is not completely understood. Solid organ transplant recipients infected with SARS-CoV-2 may have an exponential increase in thrombotic risk and the best management strategy is unknown. CASE REPORT: A female kidney transplant recipient presented with allograft's renal artery thrombosis after a recent COVID-19 infection. Due to the risk of kidney failure or exclusion, catheter directed thrombolysis was performed. Residual thrombus was excluded using an endoprosthesis with an excellent result. There were no adverse events and kidney function improved. CONCLUSION: This paper reports the endovascular treatment of renal artery thrombosis in a living-donor kidney transplant recipient with severe COVID-19 disease.

Ruptured arteriovenous fistula pseudoaneurysm treatment by balloon-assisted direct percutaneous thrombin injection.

We present the case of a male patient on hemodialysis with a ruptured pseudoaneurysm in a brachiocephalic arteriovenous fistula (AVF) and with edema and pain in the right arm attended to in the emergency department. An ultrasonographic scan identified a ruptured pseudoaneurysm with hemorrhagic infiltration of the arm muscular tissues. We performed a percutaneous ultrasound-guided thrombin injection with an angioplasty balloon inflated in the lumen of the AVF achieving the pseudoaneurysm thrombosis. After 6 months of follow-up, the patient's arteriovenous access remains functional. Percutaneous ultrasound-guided thrombin injection assisted by an angioplasty balloon may be a good alternative to surgical intervention in the treatment of symptomatic growing pseudoaneurysms of the arteriovenous fistula with the benefit of preserving the vascular access.

[18F]Atorvastatin Pharmacokinetics and Biodistribution in Healthy Female and Male Rats.

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that are widely used to prevent cardiovascular diseases. However, a series of pleiotropic mechanisms have been associated with statins, particularly with atorvastatin. Therefore, the assessment of [18F]atorvastatin kinetics with positron emission tomography (PET) may elucidate the mechanism of action of statins and the impact of sexual dimorphism, which is one of the most debated interindividual variations influencing the therapeutic efficacy. [18F]Atorvastatin was synthesized via a previously optimized 18F-deoxyfluorination strategy, used for preclinical PET studies in female and male Wistar rats (n = 7 for both groups), and for subsequent ex vivo biodistribution assessment. PET data were fitted to several pharmacokinetic models, which allowed for estimating relevant kinetic parameters. Both PET imaging and biodistribution studies showed negligible uptake of [18F]atorvastatin in all tissues compared with the primary target organ (liver), excretory pathways (kidneys and small intestine), and stomach. Uptake of [18F]atorvastatin was 38 ± 3% higher in the female liver than in the male liver. The irreversible 2-tissue compartment model showed the best fit to describe [18F]atorvastatin kinetics in the liver. A strong correlation (R2 > 0.93) between quantitative Ki (the radiotracer's unidirectional net rate of influx between compartments) and semi-quantitative liver's SUV (standard uptake value), measured between 40 to 90 min, showed potential to use the latter parameter, which circumvents the need for blood sampling as a surrogate of Ki for monitoring [18F]atorvastatin uptake. Preclinical assays showed faster uptake and clearance for female rats compared to males, seemingly related to a higher efficiency for exchanges between the arterial input and the hepatic tissue. Due to the slow [18F]atorvastatin kinetics, equilibrium between the liver and plasma concentration was not reached during the time frame studied, making it difficult to obtain sufficient and accurate kinetic information to quantitatively characterize the radiotracer pharmacokinetics over time. Nevertheless, the reported results suggest that the SUV can potentially be used as a simplified measure, provided all scans are performed at the same time point. Preclinical PET-studies with [18F]atorvastatin showed faster uptake and clearance in female compared to male rats, apparently related to higher efficiency for exchange between arterial blood and hepatic tissue.

Modular Medical Imaging Agents Based on Azide-Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of 18 F-Labeled PSMA-Tracers for Prostate Cancer Imaging.

Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide-alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide-alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting 'F-PSMA-MIC' radiotracers (t1/2 =109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [68 Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.

Emergent Endovascular Treatment in Primary Ilio-enteric Fistula.

Aortoenteric fistula (AEF) is a rare cause of gastrointestinal (GI) bleeding. If not promptly diagnosed and treated, the associated mortality is very high. The role of endovascular treatment is not yet defined. In this article, we report a clinical case of a 94-year-old male patient admitted in the emergency department with rectal bleeding. Owing to the detection of a pulsatile abdominal mass, a computed tomography angiography (CTA) scan was performed, which established the diagnosis of aorto-enteric fistula due to a left common iliac artery aneurysm (CIAA) ruptured to the sigmoid colon and also revealed an abdominal aortic aneurysm (AAA) and an internal iliac artery aneurysm (IIAA). Given the age of the patient, general condition and technical difficulty inherent to the treatment of the IIAA by conventional surgery, we chose endovascular treatment. However, we wanted to avoid contact between the endograft and the colon orifice because of the risk of infection. The patient was treated emergently with an aorto-right uni-iliac graft and a femoro-femoral bypass, IIAA embolization and 2 left iliac excluders (at the origin of the common iliac and distally in the external iliac artery). It was decided to treat colon lesion conservatively. In this case, the aorto-uni-iliac graft excluded the aortic inline flow, the distal occluder prevented retrograde flow from the external iliac, and the embolization prevented retrograde flow and treated the IIAA. This way, no arterial pressure and no prosthetic material existed inside the ruptured artery, hopefully allowing the spontaneous closing of the orifice leading the sigmoid colon to heal. The postoperative period was uneventful, and the patient was discharged at the 8th postoperative day. The patient outcome is a strong argument on the merit of the treatment strategy.

Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective.

Arginase is a widely known enzyme of the urea cycle that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. The action of arginase goes beyond the boundaries of hepatic ureogenic function, being widespread through most tissues. Two arginase isoforms coexist, the type I (Arg1) predominantly expressed in the liver and the type II (Arg2) expressed throughout extrahepatic tissues. By producing L-ornithine while competing with nitric oxide synthase (NOS) for the same substrate (L-arginine), arginase can influence the endogenous levels of polyamines, proline, and NO•. Several pathophysiological processes may deregulate arginase/NOS balance, disturbing the homeostasis and functionality of the organism. Upregulated arginase expression is associated with several pathological processes that can range from cardiovascular, immune-mediated, and tumorigenic conditions to neurodegenerative disorders. Thus, arginase is a potential biomarker of disease progression and severity and has recently been the subject of research studies regarding the therapeutic efficacy of arginase inhibitors. This review gives a comprehensive overview of the pathophysiological role of arginase and the current state of development of arginase inhibitors, discussing the potential of arginase as a molecular imaging biomarker and stimulating the development of novel specific and high-affinity arginase imaging probes.

Effectiveness and Safety of Rivaroxaban Compared to Acenocumarol after Infrainguinal Surgical Revascularization.

BACKGROUND: Optimal antithrombotic therapy after lower limb infrainguinal revascularization remains a controversial topic. The use of anticoagulants, alone or in combination with antiplatelet drugs, can potentially improve patency rate and limb salvage, particularly in patients with risk factors for early thrombosis. Bleeding is the main complication of long-term anticoagulant use. New oral anticoagulants can represent an attractive alternative to the standard vitamin K antagonists. The objective of the study is to evaluate the effectiveness (bypass occlusion and major amputation) and safety (major bleeding and all-cause mortality) of rivaroxaban compared to acenocumarol after infrainguinal lower limb surgical revascularization. MATERIAL AND METHODS: Retrospective cohort study of patients with peripheral arterial disease submitted to lower limb infrainguinal bypass revascularization with vein or expanded polytetrafluoroethylene conduit, who were anticoagulated with acenocumarol or rivaroxaban after hospital discharge. Patients with proximal revascularization, revascularization due to any pathology other than peripheral arterial disease, coagulation disorder, stroke or acute myocardial infarction in less than 30 days, glomerular filtration rate <15 mL/min, or on hemodialysis were excluded. RESULTS: One hundred nine patients were included (78.9% male), with a mean age of 64.8 years. After hospital discharge, 40 patients (36.7%) were medicated with rivaroxaban and 69 patients (63.3%) with acenocumarol. At 1 year of follow-up, patients under rivaroxaban and acenocumarol presented comparable major amputation rates (12.5 % vs. 10.1%, P = 0.756), bypass occlusion (22.5% vs. 24.6 %, P = 0.769), and mortality rate (10% vs. 8.7%, P = 0.756). Major bleeding occurred in 13.8% of patients. Patients with renal dysfunction had significantly higher bleeding risk with acenocumarol (45.5% vs. 0%, P = 0.028) compared to rivaroxaban, while patients with normal renal function presented similar bleeding rates with both anticoagulants (6.1% vs. 6.4%, P = 0.953). CONCLUSIONS: Rivaroxaban has equivalent effectiveness to acenocumarol after infrainguinal bypass revascularization, with similar occlusion, major amputation, and mortality rates. Rivaroxaban has an improved safety profile in patients with moderate renal dysfunction due to a significantly lower incidence of major bleeding. In patients with normal renal function, rivaroxaban and acenocumarol present equivalent major bleeding rates.

HAS-BLED Score Predicts the Risk of Major Bleeding in Chronic Anticoagulation after Lower Limb Surgical Revascularization.

BACKGROUND: Anticoagulant drugs are sometimes used after lower limb surgical bypass to improve patency. There are no bleeding risk scores validated specifically for patients with peripheral arterial disease. The HAS-BLED (hypertension, abnormal renal or liver function, stroke, history of or predisposition to bleeding, labile international normalized ratio (INR), elderly age [>65 years], and drugs or alcohol) score is a validated and frequently used tool to estimate the risk of major bleeding in patients receiving anticoagulation for atrial fibrillation. The objective of this study was to access the efficacy of the HAS-BLED score in predicting bleeding risk after lower limb bypass revascularization. METHODS: This study involved "secondary analysis of a retrospective database that includes patients with lower limb revascularization that was anticoagulated with acenocoumarol after hospital discharge." Consecutive patients treated between January 2014 and May 2016 were included. Patients previously on anticoagulants and patients on hemodialysis were excluded. RESULTS: Sixty-nine patients were included, 73.9% were males, with a mean age of 65 years. At 1-year follow-up, major bleeding occurred in 18.8% of patients. In this study, 52.1% of patients had HAS-BLED score ≥3. This subgroup had increased incidence of major bleeding: 33.3% compared to 0 risk factor (0%), 1 risk factor (0%), and 2 risk factors (4.2%) (P = 0.001). CONCLUSIONS: In this retrospective analysis, HAS-BLED score presented good association with major bleeding risk. It can be used as a tool for decision-making for the prescription of anticoagulants after lower limb revascularization. The prevalence of high scores is substantial, presuming high bleeding risk in this high-risk population.

Surgical Treatment of Cephalic Arch Stenosis through Rotation of the External Jugular Vein.

The percutaneous transluminal balloon angioplasty or cephalic vein transposition is the treatment for cephalic arch stenosis. In some cases, rotation of the external jugular vein may be a good option for the cephalic arch problems. We describe a new technique to treat cephalic arch stenosis. The technique enables the cephalic arch and subclavian vein to be bypassed altogether through the rotation of the external jugular vein. It consists of 3 small incisions, thus causing minimal surgical damage.

Internal Carotid Artery Tortuosity as a Rare Cause of Dysphagia: Case Report and Literature Review.

Abnormalities in the morphology of internal carotid artery are commonly identified but their natural history is not well known. Rarely, vascular abnormalities can cause mass effect causing dysphagia. We report the case of a patient presenting with long-standing dysphagia and choking during swallowing of solid food caused by an internal carotid artery tortuosity undergoing surgical treatment at our institution and we review the available literature.

Retrovirus-specificity of regulatory T cells is neither present nor required in preventing retrovirus-induced bone marrow immune pathology.

Chronic viral infections of the hematopoietic system are associated with bone marrow dysfunction, to which both virus-mediated and immune-mediated effects may contribute. Using unresolving noncytopathic Friend virus (FV) infection in mice, we showed that unregulated CD4(+) T cell response to FV caused IFN-gamma-mediated bone marrow pathology and anemia. Importantly, bone marrow pathology was triggered by relative insufficiency in regulatory T (Treg) cells and was prevented by added Treg cells, which suppressed the local IFN-gamma production by FV-specific CD4(+) T cells. We further showed that the T cell receptor (TCR) repertoire of transgenic Treg cells expressing the beta chain of an FV-specific TCR was virtually devoid of FV-specific clones. Moreover, anemia induction by virus-specific CD4(+) T cells was efficiently suppressed by virus-nonspecific Treg cells. Thus, sufficient numbers of polyclonal Treg cells may provide substantial protection against bone marrow pathology in chronic viral infections.

Structure-activity relationship study towards non-peptidic positron emission tomography (PET) radiotracer for gastrin releasing peptide receptors: Development of [18F] (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy)pyridin-2-yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamide.

Gastrin-releasing peptide receptors (GRP-Rs, also known as bombesin 2 receptors) are overexpressed in a variety of human cancers, including prostate cancer, and therefore they represent a promising target for in vivo imaging of tumors using positron emission tomography (PET). Structural modifications of the non-peptidic GRP-R antagonist PD-176252 ((S)-1a) led to the identification of the fluorinated analog (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy)pyridin-2-yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamide ((S)-1m) that showed high affinity and antagonistic properties for GRP-R. This antagonist was stable in rat plasma and towards microsomal oxidative metabolism in vitro. (S)-1m was successfully radiolabeled with fluorine-18 through a conventional radiochemistry procedure. [18F](S)-1m showed high affinity and displaceable interaction for GRP-Rs in PC3 cells in vitro.

Percutaneous Treatment Pseudo-Aneurism of the Hand in Hemophilic Patient.

INTRODUCTION: Pseudo aneurysms of the hand are infrequent lesions, usually associated with perforating trauma. The diagnosis is based on clinical suspicion and image confirmation of a pulsatile swelling. Various treatment modalities are currently described in the literature. METHODS: Presentation of a clinical case and discussion of the treatment strategy instituted. RESULTS: Clinical case: Man, 35 years old, with hemophilia A. History of perforating trauma of the palmar face of the right hand 3 weeks ago, having been sutured in the local hospital. Since then he notices a pulsatile swelling in the palm of the hand associated with paresthesias and decreased sensitivity in the index finger. A pseudo-aneurysm with 2x3cm was observed, partially thrombosed, and with probable origin in the palmar arch or in the common digital artery. He underwent angiography demonstrating the patency of the palmar arch but without perfusion of the pseudo-aneurysm, and the control dupplex scan showed complete thrombosis of the false aneurysm. After 2 months of follow-up, the dupplex scan was repeated and repermeabilization of the pseudo-aneurysm was verified. The patient was then treated with percutaneous Doppler-guided thrombin injection. Immediate thrombosis of the lesion was found, with no evidence of ischemic complications. He remained asymptomatic under clinical surveillance. CONCLUSION: For small pseudo-aneurysm conservative non- -interventional treatment with external compression may be effective. Conventional surgical treatment with simple ligation or arterial reconstruction may be indicated in larger pseudo-aneurysm. Recently, endovascular techniques such as coil embolization have also been described. Hemophilia A is a genetic disease of recessive hereditary transmission linked to the X chromosome, with deficiency of factor VIII of the coagulation cascade, which manifests with increased risk of hemorrhage. In this particular case, given the risk of hemorrhage, we chose minimally invasive percutaneous treatment, with clinical and imagological success and no complications. Percutaneous treatment by ecodoppler- guided injection of thrombin is an effective and safe treatment, particularly in pseudo-aneurysm associated with surgical risk factors.

Antiphospholipid Syndrome and Acute Postpartum Limb Ischemia.

INTRODUCTION: The diagnosis of Antiphospholipid syndrome (APS) implies the identification of antiphospoholipid antibodies and arterial/venous thrombosis or pregnancy loss. During pregnancy, there is an increased risk of thrombotic complications. METHODS: Present a case of acute lower limb ischemia in a patient with APS during postpartum period Materials/ Methods: review of a clinical case and available literature Results: Patient diagnosed with APS (triple antibody positive and antecedent of 3 previous abortions) underwent cesarean at 29 weeks of gestation. She was medicated with aspirin 00mg/day and enoxaparin 60mg/day and had discharge on the second postoperative day. After 3 days she came to the emergency department with acute limb ischemia. AngioCT revealed thrombosis of the right iliac axis and pulmonary thromboembolism. Endovenous hypocoagulation with unfractionated heparin was immediately started. Due to the high thrombotic risk associated with any type of surgical intervention and improvement of ischemia with hypocoagulation, it was decided to postpone surgical revascularization. At the 10th day of hospitalization angioCT was repeated with maintenance of the iliac thrombosis and clinically the patient had severe claudication and ankle-arm index of 0.26. On the 16th day of hospitalization (after 5 plasmapheresis sessions), she was submitted to trans-femoral thrombectomy, with a good femoral pulse at the end of the procedure. On the 3rd postoperative day we detected pulse loss and angioCT confirmed re-thrombosis of the iliac axis and an oclusion of the popliteal artery. A new attempt at revascularization was made and a new transfemoral thrombectomy was performed, with immediate pulse recovery. We performed intraoperative angiography that confirmed occlusion of the popliteal artery and we proceeded trans-popliteal thrombectomy. Intraoperative control angiography revealed permeability of ilio- -femoro-popliteal axes with some defects of filling of the crural arteries (anterior tibial and peroneal arteries). After the procedure the patient become assymptomatic, with an ankle-arm index of 0.55 (with normal flow in femoral and popliteal artery but monophasyc flow in distal arteries) and had discharged medicated with aspirin, antivitaminik K and corticoid. CONCLUSION: The beneficial/risk of revascularization surgery should be well considered as well as the timing in which it should be performed. Plasmapheresis is important to minimize the thrombotic risk associated with the surgical procedure. Intra-operative angiography is essencial since arterial thrombosis can occur in several sectors, which can conditionate the success of revascularization procedure.

Impact of Endovascular Aortic Aneurysm Repair in a Renal Transplantation Program.

BACKGROUND: An increasing number of abdominal aortic aneurysms (AAAs) may occur in renal failure patients waiting for kidney transplantation because of sharing atherosclerotic risk factors. There is increasing possibility to diagnose an AAA in this group, where treatment has some particularities. After aneurysm treatment these patients remain candidates to kidney transplantation. Similarly, there is an increasing possibility to diagnose AAA in kidney transplantation recipients. Our aim is to present our experience and review the published literature. METHODS: We studied the patients who underwent endovascular aneurysm repair (EVAR) and were later submitted to kidney transplantation, and the patients who underwent kidney transplantation and were later diagnosed with AAA and treated by EVAR. RESULTS: Our experience with renal transplantation began in 1987 and with EVAR in 2001. We performed EVAR in 3 kidney transplantation recipients, without complications as endoleaks or loss of the transplanted kidney. We performed kidney transplantation in 2 patients who underwent EVAR. CONCLUSIONS: As patients waiting for kidney transplantation wait for several months to years, necessity to treat the aortic aneurysm is sometimes imperative. EVAR is the preferred method in this high-risk group with the particularity of necessity to preserve the internal/external iliac arteries to allow anastomosis between renal artery of the transplanted kidney and recipient's iliac artery. Ensuring this, kidney transplantation remains possible and we did not detect differences in comparison with a regular procedure. Kidney transplantation recipients have some particularities as immunosuppressive therapy; in this group, EVAR was recognized as less aggressive and with less impact in renal function.

Health Literacy and Adherence to Therapy in Type 2 Diabetes: A Cross-Sectional Study in Portugal.

BACKGROUND: Therapy adherence is a key factor in the control of type 2 diabetes mellitus (T2DM). Optimal self-care requires skills in health literacy (HL). OBJECTIVE: This study aims to analyze the relationship between HL and adherence to therapy and to understand the possible influence of other sociodemographic and disease variables. METHODS: A multicenter, cross-sectional study was conducted in Portuguese in 13 different primary health care units in both rural and urban environments. A sociodemographic questionnaire and two validated instruments, "Medical Term Recognition Test" and "Summary of Diabetes Self-Care Activities," were applied. The last value of hemoglobin A1c (HbA1c) and the number of chronic medications were collected from clinical records. Descriptive statistics and bivariate correlations were performed as well as multivariable linear regression to assess the association between HL and adherence to therapy. KEY RESULTS: Participants (n = 354) were on average age 63.67 ± 10.39 years, 57.1% male and 42.9% female, 68.4% with inadequate HL and an average HbA1c of 7 ± 1.18%. Better HL was correlated with higher adherence to the total of self-care activities, nonpharmacological therapy, and foot care. In multivariable linear regression analyses, better HL (ß = 0.176, p = .003), less than minimum wage (ß = -0.197, p = .001) and insulin therapy (ß = 0.272, p = .001) were independently associated with increased adherence to overall self-care activities. CONCLUSION: In a representative sample of people with T2DM in Portugal, HL was a key factor for greater adherence to demanding self-care activities. [HLRP: Health Literacy Research and Practice. 2024;8(4):e194-e203.].

Plain Language Summary In this multicentric, cross-sectional study in Portuguese primary care, we found that better health literacy was correlated with higher adherence to the self-care activities related to type 2 diabetes, and specifically with nonpharmacological therapy and foot care. Health literacy was a key factor for greater adherence to demanding diabetes self-care activities.

Dry immersion rapidly disturbs iron metabolism in men and women: results from the VIVALDI studies.

Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity.

Synthesis and preclinical evaluation of [18F]AlF-NODA-MP-C6-CTHRSSVVC as a PET tracer for CD163-positive tumor-infiltrating macrophages.

Positron emission tomography (PET) can provide information about tumor-associated macrophage (TAM) infiltration, as long as a suitable tracer is available. This study aimed to evaluate the radiolabeled peptide [18F]AlF-NODA-MP-C6-CTHRSSVVC as a potential PET tracer for imaging of the CD163 receptor, which is expressed on M2-type tumor-associated macrophages. The conjugated peptide NODA-MP-C6-CTHRSSVVC was labeled with aluminum [18F]fluoride. Tracer binding and its biodistribution were evaluated in an in vitro binding assay and in healthy BALB/c mice, respectively. In addition, different treatments with cyclophosphamide in tumor-bearing mice were used to assess whether the tracer could detect differences in CD163 expression caused by differential TAM infiltration. After 7 days of treatment, animals were injected with [18F]AlF-NODA-MP-C6-CTHRSSVVC, and a 60-min dynamic PET scan was performed, followed by an ex vivo biodistribution study. [18F]AlF-NODA-MP-C6-CTHRSSVVC was prepared in 23 ± 6 % radiochemical yield and showed approximately 50 % of specific receptor-mediated binding in an in vitro binding assay on human CD163-expressing tissue homogenates. No CD163-mediated binding of [18F]AlF-NODA-MP-C6-CTHRSSVVC was detected by PET under normal physiological conditions in healthy BALB/c mice. On the other hand, CD163-positive xenograft tumors were clearly visualized with PET and a positive correlation was found between CD163 levels and the [18F]AlF-NODA-MP-C6-CTHRSSVVC tumor-to-muscle ratio (TMR) obtained from the PET images (Pearson r = 0.76, p = 0.002). No significant differences in the CD163 protein level and in the tracer uptake between treatment groups were found in the tumors. Taken together, [18F]AlF-NODA-MP-C6-CTHRSSVVC appears a promising candidate PET tracer for M2-type TAM, as it binds specifically to CD163 in vitro and its tumor uptake correlates well with CD163 expression in vivo.