Microenvironment M1/M2 macrophages and tumoral progression vary within C57BL/6 mice from same substrain in prostate cancer model.

Cancer mice models are critical for immune-oncology research; they provide conditions to explore tumor immunoenviroment aiming to advance knowledge and treatment development. Often, research groups breed their own mice colonies. To assess the effect of C57BL/6 mice breeding nuclei in prostate cancer development and intratumoral macrophage populations, an isotransplantation experiment was performed. C57BL/6J mice from two breeding nuclei (nA and nB) were employed for prostate adenocarcinoma TRAMP-C1 cell implantation; tumor growth period and intratumoral macrophage profile were measured. BL/6nB mice (54%) showed tumor implantation after 69-day growth period while BL/6nA implantation reached 100% across tumor growth period (28 days). No difference in total macrophage populations was observed between groups within several tumoral regions; significantly higher M2 macrophage profile was observed in tumor microenvironments from both mice groups. Nevertheless, BL/6nB tumors showed around twice the population of M1 profile (11-27%) than BL6nA (4-15%) and less non-polarized macrophages. The M1:M2 average ratio was 1:8 for group A and 1:4 for B. Our results demonstrate different tumor progression and intratumoral macrophage populations among mice from the same substrain. Data obtained in this study shows the relevance of animal source renewal for better control of murine cancer model variables.

[Long-term clinical and radiological results of metatarsophalangeal resection arthroplasty in patients with large forefoot deformities]. / Resultados clínicos y radiológicos a largo plazo de la artroplastía de resección metatarsofalángica en pacientes con grandes deformidades del antepié.

INTRODUCTION: metatarsophalangeal resection arthroplasty is considered a salvage surgical procedure able to improve the quality of life of patients with major forefoot deformities. MATERIAL AND METHODS: a retrospective observational study of 31 patients (36 feet) with major forefoot deformities operated at our institution was performed. Thirty two feet required additional surgery involving the first ray, most of them (72.2%) through MTP joint fusion. The mean follow-up period was 10.3 ± 4.6 years. Most patients were women (87.1%), the mean age was 74.2 ± 11.5 years. RESULTS: at the final follow-up, mean AOFAS score was 77.9 ± 10.2 points and mean MOxFQ score was 18.3 ± 8.3 points. Visual analog scale (VAS) for pain improved significantly from 7.5 ± 1.2 points to 3.4 ± 2.1 points on average. Good clinical results were also reported on ability to put on shoes comfortably. The mean resection arthroplasty spaces at the end of the study were 1.3, 1.8, 2.5 and 4.4 mm, for second to fifth rays, respectively. The mean sizes of remodeling osteophytes at the end of the study were 1.6, 1.4, 1.1 and 0.7 mm, respectively. Significant improvement was also achieved in the hallux valgus angle (HVA) and intermetatarsal angle (IMA) at the end of the study. CONCLUSION: in our experience, metatarsophalangeal resection arthroplasty continues to be a valid choice in patients with major forefoot deformities, with satisfactory long-term clinical and radiographic results.

INTRODUCCIÓN: la artroplastía de resección metatarsofalángica se considera un procedimiento quirúrgico de salvamento capaz de mejorar la calidad de vida de pacientes con deformidades importantes en el antepié. MATERIAL Y MÉTODOS: se realizó un estudio observacional retrospectivo de 31 pacientes (36 pies) con deformidades importantes en el antepié operados en nuestra institución. Treinta y dos pies requirieron cirugía adicional que involucró el primer metatarsiano, la mayoría de ellos (72.2%) a través de la fusión de la articulación metatarsofalángica. El período de seguimiento promedio fue 10.3 ± 4.6 años. La mayoría de los pacientes fueron mujeres (87.1%), con una edad promedio de 74.2 ± 11.5 años. RESULTADOS: en la última visita de seguimiento, la puntuación AOFAS promedio fue de 77.9 ± 10.2 puntos y la puntuación MOxFQ promedio fue de 18.3 ± 8.3 puntos. La escala visual analógica (EVA) para el dolor mejoró significativamente, pasando de 7.5 ± 1.2 puntos a 3.4 ± 2.1 puntos de media. También se constataron buenos resultados clínicos en cuanto a la capacidad de calzarse con comodidad. Los espacios de resección promedio al final del estudio fueron 1.3, 1.8, 2.5 y 4.4 mm para el segundo al quinto radio, respectivamente. Los tamaños promedio de los osteofitos por remodelación al final del estudio fueron de 1.6, 1.4, 1.1 y 0.7 mm, respectivamente. También se logró una mejora significativa en el ángulo de hallux valgus (AHV) y en el ángulo intermetatarsiano (IMA) al final del estudio. CONCLUSIÓN: en nuestra experiencia, la artroplastía de resección metatarsofalángica sigue siendo una opción válida en pacientes con deformidades graves del antepié, con resultados clínicos y radiográficos satisfactorios a largo plazo.

Rising testicular cancer incidence in Spain despite declining mortality: an age-period-cohort analysis.

BACKGROUND: Testicular cancer, primarily affecting young men, has seen an alarming rise globally. This study delves into incidence and mortality trends in Spain from 1990 to 2019 using the Global Burden of Disease (GBD) database and the Age-Period-Cohort (A-P-C) model. METHODS: We analyzed GBD data on testicular cancer cases and deaths in Spain, calculating age-standardized rates (ASIR and ASMR) and employing Joinpoint regression to identify significant shifts. The A-P-C model further dissected the effects of age, period, and birth cohort on these trends. RESULTS: A striking doubling in testicular cancer incidence was observed, from 3.09 to 5.40 per 100,000 men (1.9% annual increase), while mortality rates remained stable and even decreased in younger age groups (0.34 to 0.26 per 100,000, 0.8% annual decrease). Joinpoint analysis revealed four distinct periods of increasing incidence, with a recent slowdown. The A-P-C model highlighted a consistent rise in incidence risk with each successive generation born after 1935, contrasting with a progressive decline in mortality risk across cohorts, particularly marked for those born since the 1960s. CONCLUSION: While mortality rates are encouraging, Spain reflects the global trend of escalating testicular cancer incidence. The A-P-C analysis suggests a generational influence, but the underlying causes remain elusive. Further research is crucial to understand these trends and implement effective prevention strategies to combat this growing health concern.

Nucleic acid-loaded poly(beta-aminoester) nanoparticles for cancer nano-immuno therapeutics: the good, the bad, and the future.

Immunotherapy has emerged as a promising approach to cancer treatment, offering improved survival rates and enhanced patients' quality of life. However, realizing the full potential of immunotherapy in clinical practice remains a challenge, as there is still plenty of room for modulating the complexity of the human immune system in favor of an antitumor immunogenicity. Nanotechnology, with its unique properties, holds promise in augmenting the efficacy of cancer immunotherapies in biotherapeutic protection and site- and time-controlled delivery of the immune modulator biologicals. Polymeric nanoparticles are promising biomaterials among different nanocarriers thanks to their robustness, versatility, and cost-efficient design and production. This perspective paper overviews critical concepts in nanometric advanced delivery systems applied to cancer immunotherapy. We focus on a detailed exploration of the current state of the art and trends in using poly(beta-aminoester) (pBAE) polymers for nucleic acid-based antitumor immunotherapies. Through different examples of the use of pBAE polymers reported in the literature, we revise the main advantages these polymers offer and some challenges to overcome. Finally, the paper provides insights and predictions on the path toward the clinical implementation of cancer nano-immunotherapies, highlighting the potential of pBAE polymers for advancements in this field.

Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery.

PURPOSE: Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS). METHODS: EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. ß-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months. RESULTS: It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS. CONCLUSION: The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

Fluocinolone intravitreal implant (Iluvien) for macular edema secondary to immune recovery uveitis in patient with acute myeloid leukemia.

PURPOSE: To report the use of Fluocinolone intravitreal implant (Iluvien) for the treatment of persistent cystoid macular edema (CME) due to immune recovery uveitis syndrome in a patient with previous cytomegalovirus retinitis and acute myeloid leukemia. DESIGN: Case report. METHODS: The clinical history of a patient who received an Iluvien implant in one eye for the treatment of cystoid macular edema due to immune recovery uveitis syndrome, previously treated with peribulbar Triamcinolone and intravitreal Dexamethasone injections, was reviewed. RESULTS: A 48-year-old woman presented with cystoid macular edema due to immune recovery uveitis syndrome. The patient had a history of cytomegalovirus retinitis 3.5 years prior, secondary to immunosuppressive treatment for an acute myeloid leukemia. Three periocular triamcinolone injections and two dexamethasone intravitreal implants were performed, but the edema recurred, so fluocinolone intravitreal implant was used, achieving a sustained control of the condition at one year of follow-up. CONCLUSION: The Fluocinolone intravitreal implant may be an effective treatment for persistent CME in patients with immune recovery uveitis syndrome.

Why do patients with urinary diversions have an increased risk of bone fracture? A systematic review on risk factors for osteoporosis and bone mineral density loss in this group of patients.

INTRODUCTION: Patients undergoing radical cystectomy with urinary diversions (UD) are at increased risk of bone fractures compared to the general population. Although a loss of bone mineral density (BMD) has been described in patients with UD, we still do not know with certainty why these patients follow this tendency. OBJECTIVE: We performed a systematic review of the available literature to analyze the prevalence of osteoporosis and bone alterations in patients with ileal UD and the possible associated risk factors. EVIDENCE ACQUISITION: We systematically searched PubMed® and Cochrane Library for original articles published before December 2022 according to PRISMA guidelines. EVIDENCE SYNTHESIS: A total of 394 publications were identified. We selected 12 studies that met the inclusion criteria with 496 patients included. Six of the twelve studies showed decreased BMD values. Prevalence of osteoporosis was specified in three articles, with values ranging ​​from 0% to 36%. Risk factors such as age, sex, body mass index, metabolic acidosis and renal function appear to have an impact on bone tissue reduction, while type of UD, follow-up, 25-hydroxyvitamin D and parathormone had less evidence or contradictory data. The heterogeneity of the studies analyzed could led to interpretation bias. CONCLUSIONS: UD are associated with multiple risk factors for osteoporosis and bone fractures. Identifying patients at highest risk and establishing diagnostic protocols in routine clinical practice are essential to reduce the risk of fractures and the resulting complications.

The evolution of incisional hernia repair in Spain. A comparative analysis of results from the EVEREG registry.

BACKGROUND: The aim of this study was to assess the utility of the EVEREG registry in evaluating the evolution of surgical treatment for incisional hernia and its outcomes in Spain by comparing data from 2 study periods. METHODS: A retrospective comparative analysis of hernia surgeries performed between 2011 and 2015 (first period) and between 2017 and 2022 (second period) was conducted using data collected from the EVEREG registry. RESULTS: Statistically significant differences were observed in the second cohort, including: a decrease in minimally invasive procedures (11.7% vs 8.2%; P < .001), an increase in emergency surgeries for males (31.7% vs 41.2%; P = .017), an increase in trocar hernia repairs (16% vs 26.2%; P < .0001), a reduction in suture repairs (2.8% vs 1.5%; P < .0001), and an increase in retromuscular techniques (36.4% vs 52.4%; P < .001) in open surgery with mesh. In elective surgery, there was a decrease in the average length of stay (4.9 vs 3.8 days; P < .0001), the percentage of complications (27.9% vs 24.0%; P < .0001), reoperations (3.5% vs 1.4%; P < .0001), and mortality (0.6% vs 0.2%; P = .002). Long-term outcomes included a decrease in recurrences after 12 months (20.7% vs 14.5%; P < .0001) and in chronic pain (13.7% vs 2.5%; P < .0001) and chronic infections (9.1% vs 14.5%; P < .0001) after 6 months. CONCLUSION: In recent years, there has been a significant improvement in the outcomes of incisional hernia treatment. The registry serves as a fundamental tool for assessing the evolution of hernia treatment and enables the identification of key areas for improvement and the evaluation of treatment outcomes.

Early appearance of radiolucent lines around total knee arthroplasty in rheumatoid arthritis patients. How does it impact the aseptic failure rate and functional outcomes at 13 years of follow-up? / [Artículo traducido] Aparición temprana de líneas radiolúcidas alrededor de la artroplastia total de rodilla en pacientes con artritis reumatoide. ¿Cuál es su impacto en la tasa de fracaso aséptico y los resultados funcionales a los 13 años de seguimiento?

INTRODUCTION: Aseptic total knee arthroplasty (TKA) failure has been associated with radiolucent lines. This study aimed to determine the impact of the early appearance of radiolucent lines (linear images of 1, 2, or > 2mm at the cement-bone interface) around the TKA on prosthetic survival and functional outcomes in rheumatoid arthritis (RA) patients during a 2-20 years follow-up. METHODS: We retrospectively analyzed a consecutive series of RA patients treated with TKA between 2000 and 2011. We comparatively analyzed patients with and without radiolucent lines around implants. Clinical outcomes were assessed with the knee society score (KSS) collected before surgery, at years 2, 5, and 10, and at the last postoperative follow-up. The knee society roentgenographic evaluation system was used to analyze the impact of radiolucent lines around the implants at 1, 2, 5, and more than ten years of follow-up. The reoperation and prosthetic survival rates were calculated at the end of the follow-up. RESULTS: The study series included 72 TKAs with a median follow-up of 13.2 years (range: 4.0-21.0), of which 16 (22.2%) had radiolucent lines. We did not observe aseptic failure, and prosthetic survival at the end of the study was 94.4% (n=68). The KSS improved significantly (p<0.001) between preoperative values at 2, 5, and 10 years and the end of follow-up, with no differences between patients with and without radiolucent lines. CONCLUSIONS: Our study demonstrates that the early appearance of radiolucent lines around a TKA in RA patients does not significantly impact prosthetic survival or long-term functional outcomes at 13 years of follow-up.

Influence of laparoscopic surgery on the outcomes of radical cystectomy within a multimodal rehabilitation protocol.

INTRODUCTION AND OBJECTIVE: The implementation of Enhanced Recover After Surgery (ERAS) multimodal rehabilitation protocols in radical cystectomy has shown to improve outcomes in hospital stay and complications. The aim of this analysis is to evaluate the impact of laparoscopic surgery on radical cystectomy within a multimodal rehabilitation program. MATERIAL AND METHODS: The study was carried out in a third level center between 2011 and 2020 including patients with bladder cancer submitted to radical cystectomy according to an ERAS (Enhanced Recovery After Surgery) protocol and the Spanish Multimodal Rehabilitation Group (GERM) with 20 items to be fulfilled. RESULTS: A total of 250 radical cystectomies were performed throughout the study period, 42.8% by open surgery (OS) and 57.2% by laparoscopic surgery (LS). The groups are comparable in demographic and clinical variables (p > 0.05). Operative time was longer in the LS group (248.4 ±â€¯55.0 vs. 286.2 ±â€¯51.9 min; p < 0.001). However, bleeding was significantly lower in the LS group (417.5 ±â€¯365.7 vs. 877.9 ±â€¯529.7 cc; p < 0.001), as was the need for blood transfusion (33.6% vs. 58.9%; p < 0.001). Postoperative length of stay (11.5 ±â€¯10.5 vs. 20.1 ±â€¯17.2 days; p < 0.001), total and major complications were also significantly lower in this group (LS). The readmission rate was lower in the LS group but not significantly (36.4% vs. 29.4%; p = 0.237). The difference between 90-day mortality in both groups was not statistically significant (2.8% LS vs. 4.3% OS; p = 0.546). The differences were maintained in the multivariate models. CONCLUSIONS: Laparoscopic surgery within a multimodal rehabilitation program increases operative time but significantly decreases intraoperative bleeding, transfusion requirements, postoperative length of stay, and complications.

Management of patients with localized prostate cancer and biochemical recurrence in Spain: A medical survey.

INTRODUCTION: The management of patients with prostate cancer (PCa) is established in clinical practice guidelines, which are based on randomized studies according to the level of evidence. In Spain, the degree of compliance with these guidelines in clinical practice is unknown. OBJECTIVES: To describe the profiles of PCa patients at the time of diagnosis and the management of patients with localized PCa and those with BCR in Spain. MATERIALS & METHODS: A medical survey was conducted in specialized care (85 urologists [UROs], 64 radiation oncologists [ROs], and 21 medical oncologists [MOs]). Three questionnaires were developed for this study with 22 (UROs and ROs) or 21 questions (MOs). RESULTS: The annual incidence of PCa was 24,057 in participating hospitals (N = 131). The extrapolated annual incidence in Spain is 40,531 cases. The estimated prevalence of PCa in Spain is 221,689. Of note, 79% and 80% of patients seen by UROs and ROs, respectively had localized PCa at diagnosis. Biopsy was the most used diagnostic test among the three specialties, followed by abdominopelvic computer tomography. More than 90% of patients with BCR underwent standard tests. Next generation imaging tests and PET-choline/PSMA are still used residually. Most patients with localized PCa are currently treated with either surgery or radiotherapy, while for BCR patients, UROs and ROs prefer radiotherapy and MOs androgen deprivation therapy alone or in combination. CONCLUSION: This study describes patient profiles at the time of diagnosis and provides an overview of the current therapeutic management of localized PCa and BCR in clinical practice in Spain.

Percutaneous ablation of renal tumors: Long-term outcomes.

OBJECTIVE: To evaluate the long-term outcomes of renal tumor ablation, analyzing efficacy, long-term survival, and factors associated with complications and therapeutic success. MATERIAL AND METHODS: We retrospectively reviewed 305 ablations (generally done with expandable electrodes) of 273 renal tumors between May 2005 and April 2019. We analyzed survival, primary and secondary efficacy, and complications according to various patient factors and tumor characteristics. RESULTS: Mean blood creatinine was 1.14 mg/dL before treatment and 1.30 mg/dL after treatment (p < 0.0001). Complications were observed in 13.25% of the ablations, including major complications in in 4.97%. Complications were associated with age (p = 0.013) and tumor diameter (p < 0.0001). Primary efficacy was 96.28%. Incomplete ablation was more common in lesions measuring > 4 cm in diameter (p = 0.002). Secondary efficacy was 95.28%. The only factor associated with the risk of recurrence was the size of the tumor (p = 0.02). Overall survival was 95.26% at 1 year, 77.01% at 5 years, and 51.78% at 10 years, with no differences between patients with malignant and benign lesions. Mortality was higher in patients with creatinine >1 (p = 0.05) or ASA > 2 (p = 0.0001). CONCLUSIONS: Percutaneous ablation is extremely efficacious for renal tumors; it improves the prognosis of renal carcinoma to the point where it does not differ from that of benign lesions. Complications are rare. Like survival, complications are associated with age and overall health status.

Tox induces T cell IL-10 production in a BATF-dependent manner.

Tox is a member of the high mobility group (HMG)-Box transcription factors and plays important roles in thymic T cell development. Outside of the thymus, however, Tox is also highly expressed by CD8 and CD4 T cells in various states of activation and in settings of cancer and autoimmune disease. In CD4 T cells, Tox has been primarily studied in T follicular helper (TFH) cells where it, along with Tox2, promotes TFH differentiation by regulating key TFH-associated genes and suppressing CD4 cytotoxic T cell differentiation. However, the role of Tox in other T helper (Th) cell subtypes is less clear. Here, we show that Tox is expressed in several physiologically-activated Th subtypes and its ectopic expression enhances the in vitro differentiation of Th2 and T regulatory (Treg) cells. Tox overexpression in unpolarized Th cells also induced the expression of several genes involved in cell activation (Pdcd1), cellular trafficking (Ccl3, Ccl4, Xcl1) and suppressing inflammation (Il10) across multiple Th subtypes. We found that Tox binds the regulatory regions of these genes along with the transcription factors BATF, IRF4, and JunB and that Tox-induced expression of IL-10, but not PD-1, is BATF-dependent. Based on these data, we propose a model where Tox regulates Th cell chemotactic genes involved in facilitating dendritic cell-T cell interactions and aids in the resolution or prevention of inflammation through the production of IL-10.

[Type 3 c diabetes: Approach from the first level doctor]. / La diabetes tipo 3c. Abordaje desde el médico del primer nivel.

DM3c is diabetes (DM) of the exocrine pancreas that must be suspected whenever there is a history of chronic pancreatitis (CP), acute pancreatitis (AP) or recurrence (80% of cases) or new-onset DM in individuals from over 50 years of age without any other justification (negative autoimmunity tests, Glutamic Acid Decarboxylase antibodies). It is an entity misdiagnosed as type 2 diabetes (DM2) (90%) and therefore, if it is not suspected, it can go unnoticed. For its diagnosis, abdominal ultrasound, determination of the CA 19.9 tumor antigen (carbohydrate antigen 19-9), nuclear magnetic resonance (NMR) or computerized axial tomography (CT) are useful. The treatment is the same as DM2, although certain specifications depend on the type of drugs and with the particularity that in dealing with «fragile diabetes¼ greater caution must be taken with hypoglycemia (monitoring). Likewise, as it is a disease of the exocrine pancreas, it will have to be specifically treated to avoid metabolic, malabsorptive and/or nutritional alterations.

Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca.

BACKGROUND: Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca. METHODS: The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed. RESULTS: A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin. CONCLUSIONS: In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals.

Is unicentric familial papillary thyroid microcarcinoma different from multicentric?

BACKGROUND: Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC. DESIGN AND METHODS: Type of study: National multicenter longitudinal analytical observational study. STUDY POPULATION: Patients with FPTMC. STUDY GROUPS: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). STUDY VARIABLES: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. STATISTICAL ANALYSIS: Cox regression analysis and survival analysis. RESULTS: Ninety-four patients were included, 44% (n = 41) with unicentric FPTMC and 56% (n = 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%; p = 0.003), lymph node dissection (41 vs. 15%; p = 0.005) and therapy with radioactive iodine (96 vs. 73%; p = 0.002). Tumor stage was similar in both groups (p = 0.237), with a higher number of T3 cases in the group B (24 vs. 5%; p = 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%; p = 0.337), disease recurrence rate (21 vs. 8%; p = 0.159) and disease-free survival (p = 0.075). CONCLUSIONS: Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.

Cost-Effectiveness Analysis of 68Ga-DOTATATE PET/MRI in Radiotherapy Planning in Patients with Intermediate-Risk Meningioma.

BACKGROUND AND PURPOSE: While contrast-enhanced MR imaging is the criterion standard in meningioma diagnosis and treatment response assessment, gallium 68Ga-DOTATATE PET/MR imaging has increasingly demonstrated utility in meningioma diagnosis and management. Integrating 68Ga-DOTATATE PET/MR imaging in postsurgical radiation planning reduces the planning target volume and organ-at-risk dose. However, 68Ga-DOTATATE PET/MR imaging is not widely implemented in clinical practice due to higher perceived costs. Our study analyzes the cost-effectiveness of 68Ga-DOTATATE PET/MR imaging for postresection radiation therapy planning in patients with intermediate-risk meningioma. MATERIALS AND METHODS: We developed a decision-analytical model based on both recommended guidelines on meningioma management and our institutional experience. Markov models were implemented to estimate quality-adjusted life-years (QALY). Cost-effectiveness analyses with willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY were performed from a societal perspective. Sensitivity analyses were conducted to validate the results. Model input values were based on published literature. RESULTS: The cost-effectiveness results demonstrated that 68Ga-DOTATATE PET/MR imaging yields higher QALY (5.47 versus 5.05) at a higher cost ($404,260 versus $395,535) compared with MR imaging alone. The incremental cost-effectiveness ratio analysis determined that 68Ga-DOTATATE PET/MR imaging is cost-effective at a willingness to pay of $50,000/QALY and $100,000/QALY. Furthermore, sensitivity analyses showed that 68Ga-DOTATATE PET/MR imaging is cost-effective at $50,000/QALY ($100,000/QALY) for specificity and sensitivity values above 76% (58%) and 53% (44%), respectively. CONCLUSIONS: 68Ga-DOTATATE PET/MR imaging as an adjunct imaging technique is cost-effective in postoperative treatment planning in patients with meningiomas. Most important, the model results show that the sensitivity and specificity cost-effective thresholds of 68Ga-DOTATATE PET/MR imaging could be attained in clinical practice.