Prediction model for major bleeding in anticoagulated patients with cancer-associated venous thromboembolism using machine learning and natural language processing.

PURPOSE: We developed a predictive model to assess the risk of major bleeding (MB) within 6 months of primary venous thromboembolism (VTE) in cancer patients receiving anticoagulant treatment. We also sought to describe the prevalence and incidence of VTE in cancer patients, and to describe clinical characteristics at baseline and bleeding events during follow-up in patients receiving anticoagulants. METHODS: This observational, retrospective, and multicenter study used natural language processing and machine learning (ML), to analyze unstructured clinical data from electronic health records from nine Spanish hospitals between 2014 and 2018. All adult cancer patients with VTE receiving anticoagulants were included. Both clinically- and ML-driven feature selection was performed to identify MB predictors. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train predictive models, which were validated in a hold-out dataset and compared to the previously developed CAT-BLEED score. RESULTS: Of the 2,893,108 cancer patients screened, in-hospital VTE prevalence was 5.8% and the annual incidence ranged from 2.7 to 3.9%. We identified 21,227 patients with active cancer and VTE receiving anticoagulants (53.9% men, median age of 70 years). MB events after VTE diagnosis occurred in 10.9% of patients within the first six months. MB predictors included: hemoglobin, metastasis, age, platelets, leukocytes, and serum creatinine. The LR, DT, and RF models had AUC-ROC (95% confidence interval) values of 0.60 (0.55, 0.65), 0.60 (0.55, 0.65), and 0.61 (0.56, 0.66), respectively. These models outperformed the CAT-BLEED score with values of 0.53 (0.48, 0.59). CONCLUSIONS: Our study shows encouraging results in identifying anticoagulated patients with cancer-associated VTE who are at high risk of MB.

Fazirsiran for Adults With Alpha-1 Antitrypsin Deficiency Liver Disease: A Phase 2 Placebo Controlled Trial (SEQUOIA).

BACKGROUND & AIMS: Homozygous ZZ alpha-1 antitrypsin (AAT) deficiency produces mutant AAT (Z-AAT) proteins in hepatocytes, leading to progressive liver fibrosis. We evaluated the safety and efficacy of an investigational RNA interference therapeutic, fazirsiran, that degrades Z-AAT messenger RNA, reducing deleterious protein synthesis. METHODS: This ongoing, phase 2 study randomized 40 patients to subcutaneous placebo or fazirsiran 25, 100, or 200 mg. The primary endpoint was percent change in serum Z-AAT concentration from baseline to week 16. Patients with fibrosis on baseline liver biopsy received treatment on day 1, at week 4, and then every 12 weeks and had a second liver biopsy at or after weeks 48, 72, or 96. Patients without fibrosis received 2 doses on day 1 and at week 4. RESULTS: At week 16, least-squares mean percent declines in serum Z-AAT concentration were -61%, -83%, and -94% with fazirsiran 25, 100, and 200 mg, respectively, vs placebo (all P < .0001). Efficacy was sustained through week 52. At postdose liver biopsy, fazirsiran reduced median liver Z-AAT concentration by 93% compared with an increase of 26% with placebo. All fazirsiran-treated patients had histologic reduction from baseline in hepatic globule burden. Portal inflammation improved in 5 of 12 and 0 of 8 patients with a baseline score of >0 in the fazirsiran and placebo groups, respectively. Histologic meta-analysis of histologic data in viral hepatitis score improved by >1 point in 7 of 14 and 3 of 8 patients with fibrosis of >F0 at baseline in the fazirsiran and placebo groups, respectively. No adverse events led to discontinuation, and pulmonary function tests remained stable. CONCLUSIONS: Fazirsiran reduced serum and liver concentrations of Z-AAT in a dose-dependent manner and reduced hepatic globule burden. (ClinicalTrials.gov, Number NCT03945292).

Distribution and accumulation of UV filters (UVFs) and conservation status of Posidonia oceanica seagrass meadows in a prominent Mediterranean coastal tourist hub.

This study investigates the presence and impact of UV filters in Posidonia oceanica meadows in Formentera, a Mediterranean tourist hotspot. It highlights the distribution of inorganic (TiO2 and ZnO) and organic UV filters (UVFs) in different environmental matrices, their accumulation in seagrass tissues and their impact on the seagrass health. In the overlying and canopy waters of P. oceanica, Zn concentrations surpassed Ti, with three organic UVFs (benzophenone-3 [BP-3], avobenzone and homosalate [HMS]) consistently detected. Ti concentrations were generally higher than Zn in rhizosphere sediments, along with recurrent presence of octocrylene, HMS, 2-ethylhexyl methoxycinnamate (EHMC), and 4-methylbenzylidene camphor (4-MBC). Maximum Zn concentrations were found in canopy waters (3052.9 ng L-1). Both Ti and Zn were found in all P. oceanica tissues and leaf epiphytes across all study sites. Additional UVFs like octocrylene, avobenzone, and BP-8 were also detected in P. oceanica tissues and epiphytes. Elevated levels of octocrylene in leaf epiphytes (2112.1 ng g-1 dw) and avobenzone in leaves (364.2 ng g-1 dw) and leaf epiphytes (199.6 ng g-1 dw) were observed in the Port of La Savina, the island's main entry port. Octocrylene concentrations (up to 2575 ng g-1 dw) in rhizosphere sediments near sewage discharge points exceeded reported maxima, highlighting wastewater treatment plants as significant sources of organic UVFs. Correlational analyses suggested that the accumulation of octocrylene, avobenzone, and BP-3 negatively impacted P. oceanica's conservation status, affecting global density, density at 100 % cover, and leaf morphometry. Positive correlations were observed between leaf polyphenols (antioxidants) and concentrations of avobenzone, benzophenone-8 (BP-8), and BP-3, indicating potential oxidative stress induced by UVFs in P. oceanica. Our study underscores the pervasive presence of UV filters in P. oceanica habitats, with implications for seagrass health and conservation, especially in areas of high tourism and sewage discharge.

Clinical and Pathological Features of Osteosarcomas of the Jaws: A Retrospective Study.

INTRODUCTION: Osteosarcomas of the jaw (OSJs) are rare tumors with distinct characteristics from osteosarcomas affecting other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of OSJs. METHODS: A retrospective, descriptive cross-sectional study including patients diagnosed with OSJ registered at the "La Paz" University Hospital, Madrid, was performed. RESULTS: Data of eight patients with a diagnosis of OSJ were obtained during the study period of 22 years (2002-2024). The mean age of the patients was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most predominant histological type. Survival rate at 5 years was 50%, which decreased to 25% at 10 years. CONCLUSIONS: OSJs differ from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment. However, more studies are needed through which more standardized protocols can be proposed for adjuvant therapeutic management.

Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance. Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.

Hepatic Diffuse Large B-cell Lymphoma: A Case Report and Review of Literature of Primary Liver Tumors.

Liver tumors rank as the fourth most common cause of cancer. This case report highlights a 45-year-old female patient who presented persistent abdominal pain and no other symptoms. Initially, she was approached with a probable hepatitis of unknown origin, but her condition worsened rapidly. An endoscopic ultrasound was used to characterize the lesion, and a fine needle biopsy of the lesion was performed which revealed a diffuse large B-cell lymphoma that is CD20+ and Ki67+. Hepatic diffuse large B-cell lymphoma, as diagnosed in the patient, is a rare type of lymphoma that arises in the liver. The treatment usually involves chemotherapy, immunotherapy, and radiation therapy. However, the prognosis depends on the stage of the disease and the patient's overall health. This case reinforces the importance of considering hepatic diffuse large B-cell lymphoma in differential diagnosis for primary liver neoplasia.

Needs and Expectations of Long-Term Cancer Survivors: Multi-Centre Study Protocol.

Cancer is a social issue as its outreach affects not only mortality (it is the second cause of death in our environment) but also the costs due to morbidity and the distress it causes, as well as the losses and consequences in personal, family, work, and even social areas. This study is trying to find out the health needs of long-term cancer survivors and their perceptions and expectations of the care they received during their survival stage. For this, a joint, cross-sectional descriptive study with a qualitative and quantitative approach has been designed. For the qualitative approach, we have used different focus groups representing different geographical areas of the Spanish territory. For the qualitative approach, we have used a validated questionnaire. This study will provide a better knowledge of the quality of life of these patients, as well as their level of unmet and even unexpressed needs, in order to develop effective strategies and interventions that allow for the implementation of adapted care plans that include such unexpressed needs. This study will also allow for the creation and development of assessment methods for health results from the patient's perspective and experience. These issues require a multidisciplinary, complex approach. These survivors may require not well-known health services, as the number of these patients has grown recently, and their survival time is also longer. This research explores a wider and more thorough perspective of long-term cancer survivors' needs, experiences, and expectations to be achieved.

Acute complications in open/miss primary and revision thoracolumbar spine surgery: a descriptive study of the most common complications and treatment of choice.

PURPOSE: Main question The aim of this study is to describe and analyze the frequency of acute perioperative (intraoperatively and 30 days after) complications of open/MISS thoracolumbar spine surgery. Secondary questions A) Describe the treatment of choice for every kind of complication mentioned. B) Perform a bibliographic search and compare the complications described and their frequency with those studied in the manuscript. METHODS: A retrospective cohort of 816 patients undergoing spinal surgery over a two year period was analyzed. Acute complications of 59 patients are described whether those with a greater number of levels required longer periods of hospitalization. RESULTS: The frequency of acute complications was 7.2%. The most common was infection (2.7%), followed by dural tear (1.7%), and screw malpositioning (1%), which is consistent with the current literature. No statistically significant results were observed when comparing the mean length of hospital stay among patients operated on a greater number of levels compared to the rest (P: 0.344; 95% CI: -3.88-10.93). CONCLUSIONS: The subsidiary patient of spinal surgery is getting older and has more comorbidities, and therefore, has a higher risk of complications. Although there are models predicting the risk of complications, they are not used in routine clinical practice. It would be necessary to unify the main criteria and establish guidelines for risk detection and therapeutic algorithms based on new high-quality studies.

The c.386A>C p.(Asn129Thr) variant in SMAD4 is likely to be pathogenic, causing Juvenile Polyposis Syndrome. A case report of a mosaic variant.

BACKGROUND: Juvenile Polyposis Syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple hamartomatous gastrointestinal polyps. Here, we present a case of JPS with a mosaic variant in SMAD4. METHODS: Exome sequencing TRIO analysis, using germline DNA from the biological mother and father along with the index case (IC). RESULTS: A 46-year-old male with no family history of cancer presented with chronic iron deficiency anemia and was diagnosed with massive gastric polyposis (≥100 polyps). At the age of 59, he underwent a total gastrectomy, revealing numerous polyps occupying the entire gastric mucosa, including a 5 cm gastric hyperplastic polyp with high-grade dysplasia and focal adenocarcinoma. TRIO analysis identified the c.386A>C p.(Asn129Thr) variant in the SMAD4 gene at an allele frequency (AF) of 22%, suggesting its mosaic origin. Subsequently, the variant was found in heterozygosity in the IC's son, who exhibited two subcentimeter polyps in the colon and seven inflammatory gastric polyps with gastric inflammatory areas and hyperplasia, suggesting that the c.386A>C p.(Asn129Thr) variant in SMAD4 segregated with the phenotype. CONCLUSION: Our study provides evidence supporting the classification of the c.386A>C p.(Asn129Thr) variant in SMAD4 as a likely pathogenic variant. This finding contributes to improved accuracy in the diagnosis and genetic counseling of JPS.

The Communication of Bad News in Palliative Care: The View of Professionals in Spain.

BACKGROUND: Communication is one of the central axes around which end-of-life care revolves in the context of palliative care. Communication of bad news is reported as one of the most difficult and stressful tasks by palliative care professionals. Therefore, the aim of this study is to identify aspects related to the communication of bad news in palliative care in Spain. METHODS: Descriptive cross-sectional study. An ad hoc questionnaire was designed and sent by e-mail to all palliative care teams in Spain. RESULTS: Overall, 206 professionals (102 nurses, 88 physicians and 16 psychologists) completed the questionnaire. A total of 60.2% considered their communication of bad news skills to be good or very good. This was related to older age, experience in both the profession and palliative care, and to having received specific postgraduate training (P < .001). Around 42.2% perform communication of bad news with the patient first, which is associated with lower skill (P = .013). About 78.15% of the professionals do not use any specific protocol. CONCLUSION: This study suggests that patients access palliative care with little information about their diagnosis and prognosis. The barriers identified in the communication of bad news are the lack of specific education and training in protocol management, the difficult balance between hope and honesty, the young age of the patient, and the family.

Trehalose and Dry Eye Disease: A Comprehensive Systematic Review of Randomized Controlled Trials.

The purpose of the research project was to extensively review the efficacy and safety of a trehalose tear-substitute treatment in cases of dry eye disease (DED). A systematic review that included only full-length randomized controlled studies (RCTs) reporting the effects of trehalose tear-substitute treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included papers published before 8 August 2023. The Cochrane risk-of-bias tool was used to analyze the quality of the studies selected. A total of 10 RCTs were included in this systematic review. Trehalose tear-substitute treatments achieved a higher improvement than did control group interventions in all reported variables. The mean differences between both groups were in favor of trehalose, and were as follows: ocular surface disease index (OSDI) questionnaire score of -8.5 ± 7 points, tear film breakup time (TBUT) of 1.9 ± 1 s, tear film thickness (TFT) of 0.25 ± 0.1 µm, tear meniscus height (TMH) of 0.02 ± 0.02 mm, Schirmer test (ST) of 0.8 ± 1.4 mm, corneal fluorescein staining (CFS) of -0.7 ± 0.1 points and visual acuity (VA) of 0.3 ± 2.1 letters. No adverse events after trehalose tear-substitute treatments were reported. Trehalose tear substitutes are a safe and effective treatment for DED. Therefore, trehalose tear substitutes should be recommended for patients with dry eye disease. In addition, there is specific evidence to support its use in the preoperative cataract surgery period.

Scheimpflug Corneal Densitometry Patterns at the Graft-Host Interface in DMEK and DSAEK: A 12-Month Longitudinal Comparative Study.

BACKGROUND: To compare corneal densitometry (CD) patterns at the graft-host interface between Descemet Membrane Endothelial Keratoplasty (DMEK) and Descemet Stripping Automated Endothelial Keratoplasty (DSAEK). Corneal densitometry is a quantitative assessment that objectively evaluates corneal clarity and optical quality by measuring the light backscatter from the cornea. METHODS: Fifty-one eyes that received DMEK or DSAEK surgery for corneal endothelium dysfunction were evaluated. The primary endpoint included CD patterns at the graft-host interface, which were assessed by the Pentacam HR device at the center point of the corneal horizontal meridian (CDcentral), and at six points on the central circumference of the cornea (with a total diameter of 4 mm) (CDI,II,III,IV,V,VI). Secondary endpoints included the best-corrected distance visual acuity (BCDVA), central corneal thickness (CCT), and graft thickness (GT). All of the evaluations were performed at follow-up appointments one, three, six and twelve months after the procedure. RESULTS: DMEK showed a significant overall CD reduction of -7.9 ± 8.5 grayscale unit (GSU) compared to DSAEK (p < 0.001). In addition, the DMEK group showed significantly lower CDCentral,I,II,III,IV,V,VI values at follow-up appointments one, three, six and twelve months after the procedure compared to the DSAEK group (p < 0.001). BCDVA, CCT and GT were in favor of the DMEK group with a mean value of 0.39 ± 0.35 LogMar, 552.2 ± 71.1 µm and 11.03 ± 1.4 µm, respectively (p < 0.001). CONCLUSIONS: CD patterns at the graft-host interface seem to be different depending on the endothelial keratoplasty procedure. This provides specific insight into CD changes in this critical region of surgery, which may provide a better understanding of the postoperative evolution of these patients.

Controlling the motion of gas-lubricated adhesive disks using multiple vibration sources.

Robots capable of generating adhesion forces that can achieve free movement in application environments while overcoming their own gravity are a subject of interest for researchers. A robot with controllable adhesion could be useful in many engineered systems. Materials processing equipment, robots that climb walls, and pick-and-place machines are some examples. However, most adhesion methods either require a large energy supply system or are limited by the properties of the contact plane. For example, electromagnetic adhesion requires a ferromagnetic surface and pneumatic adhesion requires a flat surface. Furthermore, nearly all existing approaches are only used to generate adhesion forces and often require additional mechanisms to remove the adhesive component from the surface. In this study, we aimed to develop a simpler method of adhering to a surface while simultaneously moving in directions parallel to the surface, using multiple vibration sources to generate normal adhesion and propulsion. To test our approach, we constructed circular and elliptical models and conducted experiments with various inputs and model parameters. Our results show that such a gas-lubricated adhesive disk could achieve adhesive rotation and displacement in the plane without requiring any auxiliary operating system. Using only vibration sources, we were able to generate the necessary adhesion and propulsion forces to achieve the desired motion of the robot. This work represents a step towards the construction of a small-sized tetherless robot that can overcome gravity and move freely in a general environment.

Value of Prostate-Specific Antigen Kinetics in Patients with Low-Risk Prostate Cancer under Active Surveillance.

INTRODUCTION: This study analyzes the value of PSA kinetics, PSA speed (vPSA), and PSA doubling time (PSAdt), in patients with low-risk prostate cancer who are in an active surveillance (AS) program. METHODS: An observational, retrospective, and longitudinal study of a sample of 86 patients included in AS program between January 2014 and October 2021 was conducted. A review of their medical records was performed, and PSA kinetics were calculated, analyzing the causes of discontinuation of the AS program and its relationship with PSA kinetics. RESULTS: The mean age was 63.39 years, and the median follow-up was 62.55 months. The mean PSA at diagnosis was 8.27 ng/mL. A median of PSAdt of 62.55 months and 1.3 ng/mL/year for vPSA was obtained. 35 patients left the program, with a higher percentage of patients leaving with a PSAdt less than 36 months (73.7 vs. 31.1%) and a vPSA greater than 2 ng/mL/year (68.2 vs. 31.3%). The probability of permanence and the time of permanence in AS were statistically significantly higher for those patients with favorable kinetic parameters. CONCLUSION: PSA kinetics is a parameter to take into account when making decisions to keep patients in an AS program.

Development of a predictive model of venous thromboembolism recurrence in anticoagulated cancer patients using machine learning.

INTRODUCTION: Patients with cancer and venous thromboembolism (VTE) show a high risk of VTE recurrence during anticoagulant treatment. This study aimed to develop a predictive model to assess the risk of VTE recurrence within 6 months at the moment of primary VTE diagnosis in these patients. MATERIALS AND METHODS: Using the EHRead® technology, based on Natural Language Processing (NLP) and machine learning (ML), the unstructured data in electronic health records from 9 Spanish hospitals between 2014 and 2018 were extracted. Both clinically- and ML-driven feature selection were performed to identify predictors for VTE recurrence. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train different prediction models, which were subsequently validated in a hold-out data set. RESULTS: A total of 16,407 anticoagulated cancer patients with diagnosis of VTE were identified (54.4 % male and median age 70). Deep vein thrombosis, pulmonary embolism and metastases were observed in 67.2 %, 26.6 %, and 47.7 % of the patients, respectively. During the study follow-up, 11.4 % of the patients developed a recurrent VTE, being more frequent in patients with lung cancer. Feature selection and model training based on ML identified primary pulmonary embolism, deep vein thrombosis, metastasis, adenocarcinoma, hemoglobin and serum creatinine levels, platelet and leukocyte count, family history of VTE, and patients' age as predictors of VTE recurrence within 6 months of VTE diagnosis. The LR model had an AUC-ROC (95 % CI) of 0.66 (0.61, 0.70), the DT of 0.69 (0.65, 0.72) and the RF of 0.68 (0.63, 0.72). CONCLUSIONS: This is the first ML-based predictive model designed to predict 6-months VTE recurrence in patients with cancer. These results hold great potential to assist clinicians to identify the high-risk patients and improve their clinical management.

[Soy beverages and women's health: evidence review and experts opinion]. / Bebidas de soja y salud femenina. Revisión de la evidencia y opinión de expertos.

Introduction: Soy drinks are an increasingly consumed option within the Western diet. However, there are concerns about potential endocrine disruptor effects and possible impact on women's reproductive health. This review evaluates scientific documents in gynecology and obstetrics under an evidence-based medicine approach. All methods adhered to PRISMA 2020 declaration guidelines. The evaluated studies do not support a positive association between soy intake and early puberty or breast cancer; instead, a protective effect against such neoplasm was observed. Transplacental passage of soy isoflavones and their presence in breast milk has been reported without any maternal-fetal complications nor congenital malformations. Exposure to soy-derived products appears to have a neutral effect on body weight and bone health. Studies performed in adults indicate that soy may promote a minimal increase in thyrotropin (TSH) in subjects with subclinical hypothyroidism. The impact of soy-based foods on gut microbiota appears favorable, especially when consuming fermented products. Many of the human studies have been conducted with isoflavones supplements, isolated or textured soy proteins. Therefore, the results and conclusions should be interpreted cautiously, as these are not entirely applicable to commercial soy beverages.

Introducción: Las bebidas vegetales de soja constituyen una alternativa dentro de la dieta habitual. Sin embargo, existe la preocupación de potenciales efectos en la salud reproductiva de la mujer por mecanismos de disrupción endócrina. En esta revisión se evalúan documentos científicos en el área de la Ginecología y la Obstetricia bajo el tamiz de la medicina basada en la evidencia, respondiendo preguntas estructuradas. La metodología se apegó a las guías establecidas por la declaración PRISMA 2020. Los estudios evaluados descartan un riesgo incrementado de pubertad precoz o cáncer de mama; incluso se aprecia un efecto protector frente a dicha neoplasia. Se ha reportado el paso transplacentario de isoflavonas de soja y su presencia en la leche materna, sin que ello implique una relación con complicaciones materno-fetales o malformaciones congénitas. La exposición a productos de soja no parece influir sobre el peso corporal y la salud ósea de la mujer. Los estudios en adultos indican que la soja favorece un mínimo incremento de tirotropina (TSH) en personas con antecedente de hipotiroidismo subclínico. El impacto de los alimentos basados en soja sobre la microbiota intestinal parece ser favorable para su diversidad, particularmente al consumir productos fermentados. Muchos de los estudios en humanos han sido realizados con suplementos de isoflavonas o con productos que contienen proteínas aisladas o texturizadas de soja. Por tanto, los resultados y las conclusiones deben interpretarse con cautela ya que no son totalmente extrapolables a las bebidas comerciales de soja.

The contribution of penguin guano to the Southern Ocean iron pool.

Iron plays a crucial role in the high-nutrient, low-chlorophyll Southern Ocean regions, promoting phytoplankton growth and enhancing atmospheric carbon sequestration. In this area, iron-rich Antarctic krill (Euphausia superba) and baleen whale species, which are among their main predators, play a large role in the recycling of iron. However, penguins have received limited attention despite their representing the largest seabird biomass in the southern polar region. Here, we use breeding site guano volumes estimated from drone images, deep learning-powered penguin census, and guano chemical composition to assess the iron export to the Antarctic waters from one of the most abundant penguin species, the Chinstrap penguin (Pygoscelis antarcticus). Our results show that these seabirds are a relevant contributor to the iron remobilization pool in the Southern Ocean. With an average guano concentration of 3 mg iron g-1, we estimate that the Chinstrap penguin population is recycling 521 tonnes iron yr-1, representing the current iron contribution half of the amount these penguins were able to recycle four decades ago, as they have declined by more than 50% since then.

The NAFLD Decompensation Risk Score: External Validation and Comparison to Existing Models to Predict Hepatic Events in a Retrospective Cohort Study.

Background: The NAFLD decompensation risk score (the Iowa Model) was recently developed to identify patients with nonalcoholic fatty liver disease (NAFLD) at highest risk of developing hepatic events using three variables-age, platelet count, and diabetes. Aims: We performed an external validation of the Iowa Model and compared it to existing non-invasive models. Methods: We included 249 patients with NAFLD at Boston Medical Center, Boston, Massachusetts, in the external validation cohort and 949 patients in the combined internal/external validation cohort. The primary outcome was the development of hepatic events (ascites, hepatic encephalopathy, esophageal or gastric varices, or hepatocellular carcinoma). We used Cox proportional hazards to analyze the ability of the Iowa Model to predict hepatic events in the external validation (https://uihc.org/non-alcoholic-fatty-liver-disease-decompensation-risk-score-calculator). We compared the performance of the Iowa Model to the AST-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), and the FIB-4 index in the combined cohort. Results: The Iowa Model significantly predicted the development of hepatic events with hazard ratio of 2.5 [95% confidence interval (CI) 1.7-3.9, P < 0.001] and area under the receiver operating characteristic curve (AUROC) of 0.87 (CI 0.83-0.91). The AUROC of the Iowa Model (0.88, CI: 0.85-0.92) was comparable to the FIB-4 index (0.87, CI: 0.83-0.91) and higher than NFS (0.66, CI: 0.63-0.69) and APRI (0.76, CI: 0.73-0.79). Conclusions: In an urban, racially and ethnically diverse population, the Iowa Model performed well to identify NAFLD patients at higher risk for liver-related complications. The model provides the individual probability of developing hepatic events and identifies patients in need of early intervention.

Imaging in fetal genital anomalies.

Genital anomalies are a heterogeneous group of congenital pathologies that have become increasingly relevant since the Chicago Consensus of 2005. Their postnatal diagnosis has developed significantly in the last two decades, while prenatal diagnosis seems to be underdeveloped, with few protocols available, fragmented scientific literature, and low diagnostic rates. This review aims to examine the current status of this subspecialty from the perspective of prenatal imaging. Indications for the evaluation of fetal genitalia can be divided into medical and non-medical reasons. Medical reasons include sex-linked disorders, detection of other anomalies, relevant family history, or multiple pregnancy. Non-medical reasons include parental request for sex disclosure. Disclosure of fetal sex may be associated with ethical, legal, and medical issues. The main imaging technology used is 2D ultrasound, although there are other complementary techniques such as 3D, MRI, or Color Doppler. Regarding working methodology, several authors have drawn attention to the lack of standardized protocols and guidelines. Most guidelines tend to limit their recommendations to study indications and ethical issues. Technical proposals, measurements, or working methods have not yet been standardized. Fetal sex determination is usually divided into early and late gestation. Early gestation is based on the sagittal sign. Late gestation is based on direct visualization. There are several measurements to describe male and female genitalia, such as penile length, bilabial diameter, or scrotal diameter. Prenatal diagnosis of genital pathologies presents some particularities such as the wide spectrum of phenotypes, the high frequency of associated deformities, or the time of diagnosis. Some of the most frequent pathologies are ambiguous genitalia, fetal sex discordance, hypospadias, micropenis, clitoromegaly, ovarian cysts, hydro(metro)colpos, and cloacal anomalies. Higher-quality studies and direction from scientific societies through the implementation of clinical guidelines are needed.

Rational combination of SHP2 and mTOR inhibition for the treatment of hepatocellular carcinoma.

Liver cancer is the fourth most common cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the main primary malignancy affecting the liver. Unfortunately, there are still limited therapeutic options for HCC, and even the latest advances have only increased the overall survival modestly. Thus, new treatment strategies and rational drug combinations are urgently needed. Reactivation of receptor tyrosine kinases (RTK) has been described as a mechanism of intrinsic resistance to targeted therapies in a variety of cancers, including inhibitors of mTOR. The design of rational combination therapies to overcome this type of resistance is complicated by the notion that multiple RTK can be upregulated during the acquisition of resistance. SHP2, encoded by the gene PTPN11, acts downstream of virtually all RTK, and has proven to be a good target for small molecule inhibitors. Here, we report activation of multiple RTK upon mTOR inhibition in HCC which, through SHP2, leads to reactivation of the mTOR pathway. We show that co-inhibition of both mTOR and SHP2 is highly synergistic in vitro by triggering apoptosis. More importantly, the combination is well-tolerated and outperforms the monotherapies in impairing tumor growth in multiple HCC mouse models. Our findings suggest a novel rational combination therapy for the treatment of HCC.