External validation of a machine learning based algorithm to differentiate hepatic mucinous cystic neoplasms from benign hepatic cysts.

PURPOSE: To externally validate an algorithm for non-invasive differentiation of hepatic mucinous cystic neoplasms (MCN) from benign hepatic cysts (BHC), which differ in management. METHODS: Patients with cystic liver lesions pathologically confirmed as MCN or BHC between January 2005 and March 2022 from multiple institutions were retrospectively included. Five readers (2 radiologists, 3 non-radiologist physicians) independently reviewed contrast-enhanced CT or MRI examinations before tissue sampling and applied the 3-feature classification algorithm described by Hardie et al. to differentiate between MCN and BHC, which had a reported accuracy of 93.5%. The classification was then compared to the pathology results. Interreader agreement between readers across different levels of experience was evaluated with Fleiss' Kappa. RESULTS: The final cohort included 159 patients, median age of 62 years (IQR [52.0, 70.0]), 66.7% female (106). Of all patients, 89.3% (142) had BHC, and the remaining 10.7% (17) had MCN on pathology. Agreement for class designation between the radiologists was almost perfect (Fleiss' Kappa 0.840, p < 0.001). The algorithm had an accuracy of 98.1% (95% CI [94.6%, 99.6%]), a positive predictive value of 100.0% (95% CI [76.8%, 100.0%]), a negative predictive value of 97.9% (95% CI [94.1%, 99.6%]), and an area under the receiver operator characteristic curve (AUC) of 0.911 (95% CI [0.818, 1.000]). CONCLUSION: The evaluated algorithm showed similarly high diagnostic accuracy in our external, multi-institutional validation cohort. This 3-feature algorithm is easily and rapidly applied and its features are reproducible among radiologists, showing promise as a clinical decision support tool.

Fundamental frequency related parameters in Brazilians with COVID-19.

This study compares fundamental frequency (fo) and fundamental frequency standard deviation (foSD) of COVID-19 patients with the same parameters in the speech of subjects without COVID-19, and verifies whether there is an effect of age and sex in the patient group. Both groups, subjects with and without COVID-19, are formed by Brazilian Portuguese speakers. Speech samples were obtained from 100 patients with mild to severe symptoms of COVID-19, and 100 healthy subjects. A single 31-syllable Portuguese sentence was used as the elicitation material for all subjects. The recordings were divided into four age groups. The acoustic measures were semi-automatically extracted and analyzed by a series of analyses of variance. Patients with COVID-19 present vocal differences in fo-related parameters when compared to healthy subjects, that is, patient voices presented higher fo and foSD with respect to control voices. In addition, for patient voices, there was an age and sex effect on fo SD values. Vocal parameters of women and elderly subjects showed more marked differences in fo-related parameters, indicating that patient voices are higher-pitched and have a higher variation of fo SD. Consequently, fo-related parameters may be tested as vocal biomarkers in the screening of respiratory insufficiency by voice analysis, in patients with severe symptoms of COVID-19.

Multicenter External Validation of a Nomogram for Predicting Positive Prostate-specific Membrane Antigen/Positron Emission Tomography Scan in Patients with Prostate Cancer Recurrence.

BACKGROUND: A nomogram has recently been developed to predict 68Ga-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (PSMA-PET) results in recurrent prostate cancer (PCa) patients. OBJECTIVE: To perform external validation of the original nomogram in a multicentric setting. DESIGN, SETTING, AND PARTICIPANTS: A total of 1639 patients who underwent PSMA-PET for prostate-specific antigen (PSA) relapse after radical therapy were retrospectively included from six high-volume PET centers. The external cohort was stratified according to clinical setting categories: group 1: first-time biochemical recurrence (n = 774); group 2: PSA relapse after salvage therapy (n = 499); group-3: biochemical persistence after radical prostatectomy (n = 210); and group-4: advanced-stage PCa before second-line systemic therapies (n = 124). INTERVENTION: PSMA-PET in recurrent PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSMA-PET detection rate was assessed in the overall population and in each subgroup. A multivariable logistic regression model was produced to evaluate the predictors of a positive scan. The performance characteristics of the model were assessed by quantifying the predictive accuracy (PA) according to model calibration. The Youden's index was used to find the best nomogram's cutoff. Decision curve analysis (DCA) was implemented to quantify the nomogram's clinical net benefit. RESULTS AND LIMITATIONS: In the external cohort, the overall detection rate was 53.8% versus 51.2% in the original population. At multivariate analysis, International Society of Urological Pathology grade group, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.02). The PA of the nomogram was identical to the original model (82.0%); the model showed an optimal calibration curve. The best nomogram's cutoff was 55%. In the DCA, the nomogram revealed clinical net benefit when the threshold nomogram probabilities were ≥20%. The retrospective design is a major limitation. CONCLUSIONS: The original nomogram exhibited excellent characteristics on external validation. The incidence of a false negative scan can be reduced if PSMA-PET is performed when the predicted probability is ≥20%. PATIENT SUMMARY: A nomogram has been developed to predict prostate-specific membrane antigen/positron emission tomography (PSMA-PET) results for recurrent prostate cancer (PCa). The nomogram represents an easy tool in the decision-making process of recurrent PCa.

Correlation between Intensity of Pain and Disability Due to Intra-articular Lesions in Patients with Femoroacetabular Impingement Syndrome.

Objective To correlate radiographic alterations and lesions in intra-articular structures of the acetabulum with the intensity of pain and disability of patients diagnosed with femoroacetabular impingement syndrome. Methods A retrospective analysis of the preoperative data of 182 patients (190 hips) was performed. Clinical variables such as age, gender, the practice of physical activity, and radiographic variables, such as the Wiberg and alpha angles, were evaluated. Through an intraoperative video, the extent of the chondral and labial lesions was evaluated considering the clock-face method, the degree of joint involvement by the Outerbridge classification, and the presence of wave lesions. The variables were analyzed by linear regression, with the intensity of the pain assessed by the Visual Analog Scale (VAS), and functional disability measured by the Modified Harris Hip Score (mHHS). Results The mean age of the patients was of 38.5 ± 9.6 years, the mean intensity of the pain was of 7.8 ± 1.6, and the mean mHHS score was of 56.3 ± 12.7. In total, 61% of the sample were classified as Outerbridge III or IV, and 12.6% had wave lesions. There was a correlation between the male gender (r = 0.497) and lower intensity of the pain, and a correlation of age (r = -0.27), the male gender (r = 8.419) and physical activity with higher functional scores on the mHHS (r = 4.729). Conclusion There was no correlation of the radiographic and arthroscopic parameters of the present study and the intensity of pain and the disability of the patients. The male gender is related to lower intensity of pain, and higher functional ability is related to the male gender, lower age, and the practice of physical activity. Level of Evidence IV.

Correlation between Intensity of Pain and Disability Due to Intra-articular Lesions in Patients with Femoroacetabular Impingement Syndrome / Correlação entre intensidade da dor e incapacidade com as lesões intra-articulares em pacientes com síndrome do impacto femoroacetabular

Abstract Objective To correlate radiographic alterations and lesions in intra-articular structures of the acetabulum with the intensity of pain and disability of patients diagnosed with femoroacetabular impingement syndrome. Methods A retrospective analysis of the preoperative data of 182 patients (190 hips) was performed. Clinical variables such as age, gender, the practice of physical activity, and radiographic variables, such as the Wiberg and alpha angles, were evaluated. Through an intraoperative video, the extent of the chondral and labial lesions was evaluated considering the clock-face method, the degree of joint involvement by the Outerbridge classification, and the presence of wave lesions. The variables were analyzed by linear regression, with the intensity of the pain assessed by the Visual Analog Scale (VAS), and functional disability measured by the Modified Harris Hip Score (mHHS). Results The mean age of the patients was of 38.5 ± 9.6 years, the mean intensity of the pain was of 7.8 ± 1.6, and the mean mHHS score was of 56.3 ± 12.7. In total, 61% of the sample were classified as Outerbridge III or IV, and 12.6% had wave lesions. There was a correlation between the male gender (r = 0.497) and lower intensity of the pain, and a correlation of age (r = -0.27), the male gender (r = 8.419) and physical activity with higher functional scores on the mHHS (r = 4.729). Conclusion There was no correlation of the radiographic and arthroscopic parameters of the present study and the intensity of pain and the disability of the patients. The male gender is related to lower intensity of pain, and higher functional ability is related to the male gender, lower age, and the practice of physical activity. Level of Evidence IV.

Resumo Objetivo Correlacionar alterações radiográficas e lesões de estruturas intra-articulares do acetábulo com a intensidade da dor e a incapacidade de pacientes com diagnóstico de síndrome do impacto femoroacetabular. Métodos Realiou-se uma análise retrospectiva de dados pré-operatórios de 182 pacientes (190 quadris). Foram avaliadas variáveis clínicas como idade, sexo e prática de atividade física, e variáveis radiográficas, como ângulo de Wiberg e o ângulo alfa. Por meio do vídeo intraoperatório, foi avaliada a extensão das lesões condrais e labiais considerando-se o método clock-face, o grau de comprometimento articular pela classificação de Outerbridge, e a presença de lesão em onda. As variáveis foram analisadas por meio de regressão linear, tendo como variáveis dependentes a intensidade da dor, avaliada pela Escala Visual Analógica (EVA), e a incapacidade funcional, mensurada pelo Harris Hip Score modificado (HHSm). Resultados A média de idade dos pacientes foi de 38,5 ± 9,6 anos, a da intensidade da dor, 7,8 ± 1,6, e a do HHSm, 56,3 ± 12,7. No total, 61% da amostra apresentava Outerbridge III ou IV, e 12,6% apresentava lesão em onda. Observou-se correlação do sexo masculino (r = 0,497) com menor intensidade da dor, e correlação da idade (r = −0,27), do sexo masculino (r = 8,419) e da realização de atividade física com maior escore funcional no HHSm (r = 4,729). Conclusão Não houve correlação dos parâmetros radiográficos e artroscópicos deste estudo com a intensidade da dor e a incapacidade dos pacientes. O sexo masculino está relacionado com menor intensidade da dor, e maior capacidade funcional está relacionada com o sexo masculino, menor idade, e a prática de atividade física. Nível de Evidência IV.

Is There Any Difference Between a Spherical Marker and a Simple Coin for Hip Replacement Digital Planning?

Objective To evaluate the accuracy and differences between 2 types of metallic markers, sphere, and coin, for radiographic calibration in the preoperative planning of hip arthroplasty. Methods Four spherical metallic markers and four coins, both 25 mm in diameter, were placed on the greater trochanter, pubic symphysis, between the thighs, and on the table of the exam, for radiographic examination of the hip in 33 patients with hip prosthesis. The prosthesis head was used for calibration and two examiners measured the markers' image diameters, and the results were analyzed statistically. Results In the greater trochanter, the sphere and the coin were not visualized in 19 radiographs (57.6%). Between the thighs, the coin marker was not visualized in 13 radiographs (39.4%). In the greater trochanter, the 25-mm accuracy of the coin and the sphere was, respectively, between 57.1 and 63.3% and between 64.3 and 92.9%. The coin between the thighs reached 25-mm accuracy in between 50 and 60% of cases. Over the exam table, the coin and sphere markers reached, respectively, the mean diameters of 22.91 mm and 23 mm, the lowest coefficient of variation, the lowest confidence interval, and the easiest positioning. There was statistical difference between the evaluations of the markers (coin vs. sphere) in all positions ( p < 0.032), except for the exam table position ( p = 0.083). Conclusions The coin between the thighs is the best marker for radiographic calibration in the preoperative planning of hip arthroplasty, and we suggest the use of another coin on the exam table for comparison, considering the 8% reduction in relation to its real size.

Is There Any Difference Between a Spherical Marker and a Simple Coin for Hip Replacement Digital Planning? / Existe alguma diferença entre um marcador esférico e uma moeda simples para planejamento digital de substituição de quadril?

Abstract Objective To evaluate the accuracy and differences between 2 types of metallic markers, sphere, and coin, for radiographic calibration in the preoperative planning of hip arthroplasty. Methods Four spherical metallic markers and four coins, both 25 mm in diameter, were placed on the greater trochanter, pubic symphysis, between the thighs, and on the table of the exam, for radiographic examination of the hip in 33 patients with hip prosthesis. The prosthesis head was used for calibration and two examiners measured the markers' image diameters, and the results were analyzed statistically. Results In the greater trochanter, the sphere and the coin were not visualized in 19 radiographs (57.6%). Between the thighs, the coin marker was not visualized in 13 radiographs (39.4%). In the greater trochanter, the 25-mm accuracy of the coin and the sphere was, respectively, between 57.1 and 63.3% and between 64.3 and 92.9%. The coin between the thighs reached 25-mm accuracy in between 50 and 60% of cases. Over the exam table, the coin and sphere markers reached, respectively, the mean diameters of 22.91 mm and 23 mm, the lowest coefficient of variation, the lowest confidence interval, and the easiest positioning. There was statistical difference between the evaluations of the markers (coin vs. sphere) in all positions (p< 0.032), except for the exam table position (p= 0.083). Conclusions The coin between the thighs is the best marker for radiographic calibration in the preoperative planning of hip arthroplasty, and we suggest the use of another coin on the exam table for comparison, considering the 8% reduction in relation to its real size.

Resumo Objetivo Avaliar a precisão e as diferenças entre 2 tipos de marcadores metálicos, esfera e moeda, para calibração radiográfica no planejamento pré-operatório da artroplastia de quadril. Métodos Quatro marcadores metálicos esféricos e quatro moedas, ambas de 25 mm de diâmetro, foram colocadas em trocânter maior, sínfise púbica, entre as coxas e a mesa do exame, para exame radiográfico do quadril em 33 pacientes com prótese de quadril. A cabeça da prótese foi utilizada para calibração e dois examinadores mediram os diâmetros da imagem dos marcadores, e os resultados foram analisados estatisticamente. Resultados No trocânter maior, a esfera e a moeda não foram visualizadas em 19 radiografias (57,6%). Entre as coxas, o marcador de moeda não foi visualizado em 13 radiografias (39,4%). No trocânter maior, a precisão de 25 mm da moeda e da esfera foi, respectivamente, entre 57,1 e 63,3% e entre 64,3 e 92,9%. A moeda entre as coxas atingiu 25 mm de precisão entre 50 e 60%. Sobre a mesa de exame, os marcadores de moeda e esfera atingiram, respectivamente, diâmetros médios de 22,91 mm e 23 mm, o menor coeficiente de variação, o menor intervalo de confiança e o posicionamento mais fácil. Houve diferença estatística entre as avaliações dos marcadores (moeda vs. esfera) em todas as posições (p< 0,032), com exceção da posição na mesa de exame (p= 0,083). Conclusões A moeda entre as coxas é o melhor marcador para calibração radiográfica no planejamento pré-operatório da artroplastia de quadril, e sugerimos o uso de outra moeda na mesa de exame para comparação, considerando os 8% de redução em relação ao seu tamanho real.

Exacerbated Renal and Hematologic Toxicities to Ifosfamide and Doxorubicin-Based Chemotherapy in a Patient with Retroperitoneal Liposarcoma Harboring a Germline Mutation in the WRN Gene.

Werner's syndrome is caused by the inactivation of both WRN alleles and is characterized by premature aging and increased risk of neoplasms, especially those of mesenchymal origins, such as sarcomas. Given the characteristic genomic instability, patients with this syndrome are more susceptible to develop toxicities when exposed to cytotoxic agents, such as alkylators and anthracyclines. The impact of the monoallelic WRN mutation on treatment-associated toxicities is poorly understood. Here, we report a patient with locally advanced dedifferentiated liposarcoma of the retroperitoneum harboring a heterozygous germline inactivation mutation in the WRN gene, who was treated with a classic regimen of ifosfamide and doxorubicin and developed exacerbated and prolonged hematological and renal toxicities.

Value of Primary Rectal Tumor PET/MRI in the Prediction of Synchronic Metastatic Disease.

PURPOSE: To analyze the associations between positron emission tomography (PET)/magnetic resonance imaging (MRI) features for primary rectal tumors and metastases. PROCEDURES: Between November 2016 and April 2018, 101 patients with rectal adenocarcinoma were included in this prospective study (NCT02537340) for whole-body PET/MRI for baseline staging. Two readers analyzed the PET/MRI; they assessed the semiquantitative PET features of the primary tumor and the N- and M-stages. Another reader analyzed the MRI features for locoregional staging. The reference standard for confirming metastatic disease was biopsy or imaging follow-up. Non-parametric tests were used to compare the PET/MRI features of the participants with or without metastatic disease. Binary logistic regression was used to evaluate the associations between the primary tumor PET/MRI features and metastatic disease. RESULTS: A total of 101 consecutive participants (median age 62 years; range: 33-87 years) were included. Metastases were detected in 35.6% (36 of 101) of the participants. Among the PET/MRI features, higher tumor lesion glycolysis (352.95 vs 242.70; P = .46) and metabolic tumor volume (36.15 vs 26.20; P = .03) were more frequent in patients with than in those without metastases. Additionally, patients with metastases had a higher incidence of PET-positive (64% vs 32%; P = .009) and MRI-positive (56% vs 32%; P = .03) mesorectal lymph nodes, extramural vascular invasion (86% vs 49%; P > .001), and involvement of mesorectal fascia (64% vs 42%; P = .04); there were also differences between the mrT stages of these two groups (P = .008). No differences in the maximum standardized uptake values for the primary tumors in patients with and without metastases were observed (18.9 vs 19.1; P = .56). Multivariable logistic regression showed that extramural vascular invasion on MRI was the only significant predictor (adjusted odds ratio, 3.8 [95% CI: 1.1, 13.9]; P = .001). CONCLUSION: PET/MRI facilitated the identification of participants with a high risk of metastatic disease, though these findings were based mainly on MRI features.

Luteolin Improves Perivascular Adipose Tissue Profile and Vascular Dysfunction in Goto-Kakizaki Rats.

We investigated the effects of luteolin on metabolism, vascular reactivity, and perivascular adipose tissue (PVAT) in nonobese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats. METHODS: Wistar and GK rats were divided in two groups: (1) control groups treated with vehicle; (2) groups treated with luteolin (10 mg/kg/day, for 2 months). Several metabolic parameters such as adiposity index, lipid profile, fasting glucose levels, glucose and insulin tolerance tests were determined. Endothelial function and contraction studies were performed in aortas with (PVAT+) or without (PVAT-) periaortic adipose tissue. We also studied vascular oxidative stress, glycation and assessed CRP, CCL2, and nitrotyrosine levels in PVAT. RESULTS: Endothelial function was impaired in diabetic GK rats (47% (GK - PVAT) and 65% (GK + PVAT) inhibition of maximal endothelial dependent relaxation) and significantly improved by luteolin treatment (29% (GK - PVAT) and 22% (GK + PVAT) inhibition of maximal endothelial dependent relaxation, p < 0.01). Vascular oxidative stress and advanced glycation end-products' levels were increased in aortic rings (~2-fold, p < 0.05) of diabetic rats and significantly improved by luteolin treatment (to levels not significantly different from controls). Periaortic adipose tissue anti-contractile action was significantly rescued with luteolin administration (p < 0.001). In addition, luteolin treatment significantly recovered proinflammatory and pro-oxidant PVAT phenotype, and improved systemic and metabolic parameters in GK rats. CONCLUSIONS: Luteolin ameliorates endothelial dysfunction in type 2 diabetes and exhibits therapeutic potential for the treatment of vascular complications associated with type 2 diabetes.

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

BACKGROUND: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use. METHODS: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered. RESULTS: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies. CONCLUSION: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.

Augmented Reality in Orthopedic Surgery Is Emerging from Proof of Concept Towards Clinical Studies: a Literature Review Explaining the Technology and Current State of the Art.

PURPOSE OF REVIEW: Augmented reality (AR) is becoming increasingly popular in modern-day medicine. Computer-driven tools are progressively integrated into clinical and surgical procedures. The purpose of this review was to provide a comprehensive overview of the current technology and its challenges based on recent literature mainly focusing on clinical, cadaver, and innovative sawbone studies in the field of orthopedic surgery. The most relevant literature was selected according to clinical and innovational relevance and is summarized. RECENT FINDINGS: Augmented reality applications in orthopedic surgery are increasingly reported. In this review, we summarize basic principles of AR including data preparation, visualization, and registration/tracking and present recently published clinical applications in the area of spine, osteotomies, arthroplasty, trauma, and orthopedic oncology. Higher accuracy in surgical execution, reduction of radiation exposure, and decreased surgery time are major findings presented in the literature. In light of the tremendous progress of technological developments in modern-day medicine and emerging numbers of research groups working on the implementation of AR in routine clinical procedures, we expect the AR technology soon to be implemented as standard devices in orthopedic surgery.

Patient Education in Orthopedics: the Role of Information Design and User Experience.

PURPOSE OF REVIEW: This narrative review will focus on concepts and methods of Information Design and User Experience for patient education in orthopedics, with osteoarthritis as an application example. RECENT FINDINGS: Information design can make complex health information clear according to the needs of the patients. Digital health presents new opportunities to design scalable educational interventions and may be improved with User Experience Design. Human-centered design methods such as user research, co-design, and prototype testing are being applied in orthopedics to achieve patient-centered care. Current international guidelines on osteoarthritis put patient education as one of the key care strategies. Educational interventions target preoperative education and osteoarthritis self-management, but current models could be enhanced. Patient education and health literacy are fundamental to face the burden of musculoskeletal pain. The collaboration between design and health is essential to deal with the demand for education, behavioral, and social change.

Diagnostic accuracy of FDG-PET/MRI versus pelvic MRI and thoracic and abdominal CT for detecting synchronous distant metastases in rectal cancer patients.

PURPOSE: We compared the diagnostic accuracy of detecting distant metastases for baseline rectal cancer staging between PET/MRI and conventional staging (CS). MATERIALS AND METHODS: This prospective study from November 2016 to April 2018 included 101 rectal adenocarcinoma patients for primary staging. These patients underwent whole-body PET/MRI in addition to CS (pelvic MRI and thoracic and abdominal contrast-enhanced CT). Different readers analyzed CS and PET/MRI findings for primary tumor, nodal, and metastatic staging. The presence, number, and location of metastases were recorded according to the organ involved (non-regional lymph nodes (LNs), liver, lungs, or others). Lesions were defined as positive, negative, or indeterminate. The number of lesions per organ was limited to 10. The McNemar test was used to compare the accuracies. RESULTS: PET/MRI exhibited a higher accuracy in detecting metastatic disease than CS in all patients (88.4% vs. 82.6%, p = 0.003) and in patients with extramural vascular invasion (EMVI) (88.9% vs. 85.5%, p = 0.013). The detection rate of PET/MRI was superior to that of CS for all lesions [84.1% vs. 68.9%, p = 0.001], as well as those in the liver (89.2% vs. 84.2%), non-regional LNs (90.0% vs. 36.7%), and lungs (76.4% vs. 66.9%). PET/MRI correctly classified 19/33 (57.5%) patients with indeterminate lesions on CS. CONCLUSION: PET/MRI yields higher accuracy than CS for detecting distant synchronous metastases in the baseline staging of patients with rectal cancer and EMVI. PET/MRI exhibited a higher detection rate than CS for identifying non-regional LNs, hepatic lesions, and pulmonary lesions as well as correctly classifying patients with indeterminate lesions. TRIAL REGISTRATION: NCT02537340.

Omentin: A novel therapeutic approach for the treatment of endothelial dysfunction in type 2 diabetes.

BACKGROUND: Perivascular adipose tissue (PVAT) locally influences the functioning of blood vessels and promotes vascular complications associated with diabetes and obesity. The aim of this work was to study the impact of omentin-1 on endothelial function and PVAT in a non-obese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats with or without high fat diet. MATERIAL AND METHODS: Diabetic GK rats were divided into four groups: 1) control group; 2) group treated with omentin-1; 3) group of GK rats fed a high fat diet (GKHFD) and 4) group of GKHFD treated with omentin-1. Several in vivo parameters such as adiposity and Lee indexes, lipid profile, fasting glucose levels, glucose and insulin tolerance tests were determined. At the vascular level, endothelial dependent and independent relaxation and contraction studies were performed in aortic rings in the absence (PVAT-) or in the presence (PVAT+) of thoracic PVAT. We also evaluated vascular oxidative stress and determined the pro-inflammatory status of PVAT. RESULTS: Endothelium-dependent relaxation to acetylcholine, assessed by wire myography, was impaired in GK and GKHFD rats and improved by the omentin-1 treatment. In addition, vascular superoxide production was increased in the vascular wall of diabetic rats, accompanied by reduced nitric oxide bioavailability and significantly improved by omentin treatment. PVAT anti-contractile action found under physiological conditions was lost in type 2 diabetes, and partially recovered with omentin-1 administration. In addition, omentin-1 treatment significantly improved proinflammatory and pro-oxidant PVAT phenotype (decreasing C-reactive protein and nitrotyrosine levels). Furthermore, it was observed an improvement in various systemic and metabolic biochemical parameters of diabetic animals treated for one month with omentin. CONCLUSIONS: Omentin-1 ameliorates endothelial dysfunction in type 2 diabetes and presents therapeutic potential for the treatment of vascular complications associated with type 2 diabetes.

Reassessing Patterns of Response to Immunotherapy with PET: From Morphology to Metabolism.

Cancer demands precise evaluation and accurate and timely assessment of response to treatment. Imaging must be performed early during therapy to allow adjustments to the course of treatment. For decades, cross-sectional imaging provided these answers, showing responses to the treatment through changes in tumor size. However, with the emergence of immune checkpoint inhibitors, complex immune response patterns were revealed that have quickly highlighted the limitations of this approach. Patterns of response beyond tumor size have been recognized and include cystic degeneration, necrosis, hemorrhage, and cavitation. Furthermore, new unique patterns of response have surfaced, like pseudoprogression and hyperprogression, while other patterns were shown to be deceptive, such as unconfirmed progressive disease. This evolution led to new therapeutic evaluation criteria adapted specifically for immunotherapy. Moreover, inflammatory adverse effects of the immune checkpoint blockade were identified, many of which were life threatening and requiring prompt intervention. Given complex concepts like tumor microenvironment and novel therapeutic modalities in the era of personalized medicine, increasingly sophisticated imaging techniques are required to address the intricate patterns of behavior of different neoplasms. Fluorine 18-fluorodeoxyglucose PET/CT has rapidly emerged as one such technique that spans both molecular biology and immunology. This imaging technique is potentially capable of identifying and tracking prognostic biomarkers owing to its combined use of anatomic and metabolic imaging, which enables it to characterize biologic processes in vivo. This tailored approach may provide whole-body quantification of the metabolic burden of disease, providing enhanced prediction of treatment response and improved detection of adverse events. ©RSNA, 2020.

PET/MRI Characterization of Mucinous Versus Nonmucinous Components of Rectal Adenocarcinoma: A Comparison of Tumor Metabolism and Cellularity.

OBJECTIVE. The purpose of this study was to evaluate whether FDG PET/MRI can be used to differentiate the mucinous from the nonmucinous components of primary rectal tumors and to compare the glycolytic metabolism on PET with tumor cellularity on DWI in both components. SUBJECTS AND METHODS. Ninety-nine patients who underwent FDG PET/MRI for staging of primary rectal cancer were included in this prospective analysis. MRI depicted the mucin component through the tumor volume. Separate volumes of interest were drawn on both mucinous and nonmucinous components and propagated to PET and apparent diffusion coefficient (ADC) mapping. Maximum and mean standardized uptake values (SUVmax, SUVmean) and maximum, mean, and minimum ADC values (ADCmax, ADCmean, ADCmin) were recorded and compared between areas with mucinous and nonmucinous components. Whole-body PET/MRI was also used to evaluate for the presence of distant metastases. Nonparametric testing was used to compare the two groups of patients: those with tumors with a mucinous component and those with tumors without a mucinous component. Logistic regression analysis was performed to calculate the association risk between mucinous component and metastatic disease. RESULTS. Seventeen patients (17.2%) had a mucinous component within the tumor on T2-weighted MRI. Most of these patients had advanced disease, the mucinous component tumors being in significantly higher T categories than the tumors without a mucinous component (88.2% vs 61.0%; p = 0.032). SUVmax (7.4 vs 16.7; p = 0.002) and SUVmean (5.4 vs 13.4; p = 0.001) were significantly lower in tumors with a mucinous component than in those without a mucinous component. Tumor ADC measurements were not different between tumors with and those without a mucinous component (ADCmean, 1.4 vs 1.6; p = 0.361). There was no association between presence of a mucinous component within the primary rectal tumor and presence of synchronous metastases (odds ratio, 1.1 [0.4-3.0]; p = 0.904). Moreover, the occurrence of metastases in patients with mucinous component tumors (7/17 [41.2%]) was not different from that in patients with tumors without a mucinous component (28/82 [34.1%]) (p = 0.887). CONCLUSION. PET/MRI can be used to differentiate the mucinous and nonmucinous components within primary rectal adenocarcinoma on the basis of metabolic status. The FDG uptake is significantly lower in the mucinous component, but tumor cellularity based on MRI and DWI findings is not. Despite being associated with a higher T category in the sample of patients in this study, the presence of a mucinous component seems not to be associated with increased risk of synchronous metastases.