Social Impacts of the COVID-19 Pandemic on Women's Health in the Greater Los Angeles Area.

Background: Since the COVID-19 pandemic started, women have experienced more job loss owing to an increase in household and caregiving responsibilities. Gender inequities coupled with pandemic-related stressors have resulted in poor health outcomes among women. Globally, women have reported higher levels of anxiety, depression, and stress in response to the pandemic. Evidence suggests that social determinants of health have contributed to women's poor health outcomes. Materials and Methods: We used the Understanding America Study to describe the social impacts women have experienced during the COVID-19 pandemic when compared with men and to explore the association between partnership status and social impacts in Los Angeles. We hypothesize that women experienced greater social impacts than men and that partnership status modified these social impacts. Results: In a sample of predominantly racial and ethnic minorities, we found that women experienced more social impacts related to housing insecurity compared with men. When exploring how partnership status modified these social impacts, we found that women without partners experienced more social impacts specific to financial hardships when compared with women who were in a partnership. Conclusions: It is likely that the COVID-19 relief efforts helped women mitigate social impacts but not housing or financial security. The overall goal is to inform policies so that better measures can be implemented to prepare for the next public health disaster or global health threat.

68Ga-DOTA-D-Alanine-BoroPro Radiotracer for Imaging of the Fibroblast Activation Protein in Malignant and Non-Malignant Diseases.

Recently, we reported a new fibroblast activation protein (FAP) inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-HYNIC-D-Alanine-BoroPro)(99mTc-HYNIC-iFAP) structure for tumor microenvironment SPECT imaging. This research aimed to synthesize 68Ga-[2,2',2″,2‴-(2-(4-(2-(5-(((S)-1-((S)-2-boronopyrrolidin-1-yl)-1-oxopropan-2-yl)carbamoyl)pyridin-2-yl)hydrazine-1-carbothioamido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid] (68Ga-DOTA-D-Alanine-BoroPro)(68Ga-iFAP) as a novel radiotracer for PET imaging and evaluate its usefulness for FAP expression in malignant and non-malignant tissues. The coupling of p-SCN-benzene DOTA with HYNIC-iFAP was used for the chemical synthesis and further labeling with 68Ga. Radiochemical purity was verified by radio-HPLC. The specificity of 68Ga-iFAP was evaluated in HCT116 cells, in which FAP expression was verified by immunofluorescence and Western blot. Biodistribution and biokinetic studies were performed in murine models. 68Ga-iFAP uptake at the myocardial level was assessed in mice with induced infarction. First-in-human images of 68Ga-iFAP in healthy subjects and patients with myocardial infarction, glioblastoma, prostate cancer, and breast cancer were also obtained. DOTA-D-Alanine BoroPro was prepared with a chemical purity of 98% and was characterized by UPLC mass spectroscopy, FT-IR, and UV-vis. The 68Ga-iFAP was obtained with a radiochemical purity of >95%. In vitro and in vivo studies demonstrated 68Ga-iFAP-specific recognition for FAP, rapid renal elimination, and adequate visualization of the glioblastoma, breast tumor, prostate cancer, and myocardial infarction sites. The results of this research justify further dosimetry and clinical trials to establish the specificity and sensitivity of 68Ga-iFAP PET for FAP expression imaging.

[Translated article] Retrospective study of home antibiotic infusion therapy using elastomeric infusion pumps.

OBJECTIVES: To describe the experience of home antibiotic infusion therapy using elastomeric infusion pumps, administered to patients admitted to the Home Hospitalisation Unit of a tertiary hospital for 3 years and to analyse clinical evolution and mortality. METHOD: Retrospective observational study. The medical history of the patients included in the study was reviewed. Information was obtained on personal history, antimicrobial therapy received, and clinical evolution. Statistical analysis was performed using SPSS® 19 software. RESULTS: 81 patients were included, 61.7% men, with a mean age of 73.5±17.5 years. The most frequent comorbidities were diabetes mellitus (30.9%) and chronic kidney disease (28.4%). Patients received a mean of 11.9±8.5 days of antibiotic treatment in an elastomeric infusion pump. The main focus of infection was respiratory (27.2%), followed by bacteremia (16%) and skin and soft tissue infections (12.3%). Of the infections, 65.4% were monomicrobial, with Pseudomonas aeruginosa being the main microorganism involved (39.6%). The most commonly used antimicrobial was piperacillin/tazobactam (33.3%). The clinical course was good in 85.2% of the patients, but the mortality rate in the 30 days following the end of treatment was 24.7%. In the univariate analysis, a history of neoplasia in the last 5 years (p=.01) and having received fewer days of antibiotic therapy prior to the start of outpatient antimicrobial therapy in infusion pump (p=.04) were associated with worse clinical outcome. Age over 80 years was associated with better outcome (p=.03). The diagnosis of heart failure was associated with higher mortality (p=.026) and patients from surgical services, with lower mortality (p=.047). In the multivariate analysis, the presence of neoplasia was associated with unfavourable evolution (p=.012) and heart failure with higher mortality (p=.027). CONCLUSIONS: Outpatient antimicrobial therapy in elastomeric infusion pumps is an alternative in patients requiring prolonged intravenous treatment, and age is not a conditioning factor for inclusion in these programs. However, the presence of certain comorbidities can negatively affect the clinical course and mortality of patients.

BCGitis con afectación de aneurisma aortoilíaco: aportación de dos casos y revisión de la literatura / BCGitis with aortoiliac aneurysm involvement: Report of two cases and review of the literature

La BCGitis es una complicación infrecuente del tratamiento intravesical con Bacillus Calmette-Guérin para el cáncer superficial de vejiga de alto grado y el carcinoma in situ. Puede causar afectación vascular. Presentamos 2 casos y una revisión de la literatura de series de casos publicadas en los 10 años previos a la finalización de este trabajo en abril de 2022, que describiesen un caso de aneurisma micótico aortoilíaco tras recibir este tratamiento. De los 51 casos incluidos (49 revisados y 2 originales), el 100% eran hombres, 82% tenían más de 65 años. La mediana del período de latencia fue de 15 meses (RIQ 18). La localización más frecuente fue la aorta abdominal, documentándose rotura en el 45,1%. El síntoma más frecuente fue dolor abdominal o lumbar (61%), seguido de síndrome general (49%). Asoció absceso retroperitoneal un 39,2%. La mortalidad atribuible fue de 13,6%. La BCGitis debería incluirse como diagnóstico diferencial de pacientes que hayan recibido terapia con BCG y presenten afectación vascular, incluso años tras el tratamiento.(AU)

BCGitis is a rare complication after intravesical administration of Bacillus Calmette-Guérin for high-grade superficial bladder cancer and carcinoma in situ. May cause vascular involvement. We present two cases and a review of the literature of the case reports published on the 10 years prior to April of 2022, when this project was finished, which described a case of aortoiliac mycotic aneurysm after receiving this treatment. Of the 51 cases included (49 revised and 2 original), 100% were men, 82% were older than 65 years. The median latency period was 15 months (IQR 18). The most frequent location was the abdominal aorta, rupture occurred in 45.1% of patients. The most frequent symptom was abdominal or lumbar pain (61%), followed by general syndrome (49%). In 39.2% cases, it was associated with retroperitoneal abscesses. Attributable mortality was 13.6%. BCGitis should be included in the differential diagnosis in patients who have received BCG therapy and present vascular involvement, even years after being treated.(AU)

Computer vision enables taxon-specific identification of African carnivore tooth marks on bone.

Taphonomic works aim at discovering how paleontological and archaeofaunal assemblages were formed. They also aim at determining how hominin fossils were preserved or destroyed. Hominins and other mammal carnivores have been co-evolving, at least during the past two million years, and their potential interactions determined the evolution of human behavior. In order to understand all this, taxon-specific carnivore agency must be effectively identified in the fossil record. Until now, taphonomists have been able to determine, to some degree, hominin and carnivore inputs in site formation, and their interactions in the modification of part of those assemblages. However, the inability to determine agency more specifically has hampered the development of taphonomic research, whose methods are virtually identical to those used several decades ago (lagged by a high degree of subjectivity). A call for more objective and agent-specific methods would be a major contribution to the advancement of taphonomic research. Here, we present one of these advances. The use of computer vision (CV) on a large data set of images of tooth marks has enabled the objective discrimination of taxon-specific carnivore agency up to 88% of the testing sample. We highlight the significance of this method in an interdisciplinary interplay between traditional taphonomic-paleontological analysis and artificial intelligence-based computer science. The new questions that can be addressed with this will certainly bring important changes to several ideas on important aspects of the human evolutionary process.

Pharmaceutical Nanoplatforms Based on Self-nanoemulsifying Drug Delivery Systems for Optimal Transport and Co-delivery of siRNAs and Anticancer Drugs.

Small interfering RNAs (siRNAs) have the ability to induce selective gene silencing, although siRNAs are vulnerable to degradation in vivo. Various active pharmaceutical ingredients (APIs) are currently used as effective therapeutics in the treatment of cancer. However, routes of administration are limited due to their physicochemical and biopharmaceutical properties. This research aimed to develop oral pharmaceutical formulations based on self-nanoemulsifying drug delivery systems (SNEDDS) for optimal transport and co-delivery of siRNAs related to cancer and APIs. Formulations were developed using optimal mixing design (Design-Expert 11 software) for SNEDDS loading with siRNA (water/oil emulsion), API (oil/water emulsion), and siRNA-API (multiphase water/oil/water emulsion). The final formulations were characterized physicochemically and biologically. The nanosystems less than 50 nm in size had a drug loading above 48 %. The highest drug release occurred at intestinal pH, allowing drug protection in physiological fluids. SNEDDS-siRNA-APIs showed a twofold toxicity effect than APIs in solution and higher transfection and internalization of siRNA in cancer cells with respect to free siRNAs. In the duodenum, higher permeability was observed with SNEDDS-API than with the API solution, as determined by ex-vivo fluorescence microscopy. The multifunctional formulation based on SNEDDS was successfully prepared, siRNA, hydrophobic chemotherapeutics (doxorubicin, valrubicin and methotrexate) and photosensitizers (rhodamine b and protoporphyrin IX) agents were loaded, using a chitosan-RNA core, and Labrafil® M 1944 CS, Cremophor® RH40, phosphatidylcholine shell, forming stable hybrid SNEDDS as multiphasic emulsion, suitable as co-delivery system with a potent anticancer activity.

Retrospective study of home antibiotic infusion therapy in elastomeric infusion pumps. / Estudio retrospectivo de la terapia de infusión de antibióticos domiciliaria en bombas de infusión elastoméricas.

OBJECTIVES: To describe the experience of home antibiotic infusion therapy using elastomeric infusion pumps, administered to patients admitted to the Home Hospitalization Unit of a tertiary hospital for three years and to analyse clinical evolution and mortality. METHOD: Retrospective observational study. The medical history of the patients included in the study was reviewed. Information was obtained on personal history, antimicrobial therapy received and clinical evolution. Statistical analysis was performed using SPSS® 19 software. RESULTS: Eighty-one patients were included, 61.7% men, with a mean age of 73.5 ± 17.5 years. The most frequent comorbidities were diabetes mellitus (30.9%) and chronic kidney disease (28.4%). Patients received a mean of 11.9 ± 8.5 days of antibiotic treatment in an elastomeric infusion pump. The main focus of infection was respiratory (27.2%), followed by bacteremia (16%) and skin and soft tissue infections (12.3%). Of the infections, 65.4% were monomicrobial, with Pseudomonas aeruginosa being the main microorganism involved (39.6%). The most commonly used antimicrobial was piperacillin/tazobactam (33.3%). The clinical course was good in 85.2% of the patients, but the mortality rate in the 30 days following the end of treatment was 24.7%. In the univariate analysis, a history of neoplasia in the last 5 years (p = 0.01) and having received fewer days of antibiotic therapy prior to the start of outpatient antimicrobial therapy in infusion pump (p = 0.04) were associated with worse clinical outcome. Age over 80 years was associated with better outcome (p = 0.03). The diagnosis of heart failure was associated with higher mortality (p = 0.026) and patients from surgical services, with lower mortality (p = 0.047). In the multivariate analysis, the presence of neoplasia was associated with unfavorable evolution (p = 0.012) and heart failure with higher mortality (p = 0.027). CONCLUSIONS: Outpatient antimicrobial therapy in elastomeric infusion pumps is an alternative in patients requiring prolonged intravenous treatment, and age is not a conditioning factor for inclusion in these programs. However, the presence of certain comorbidities can negatively affect the clinical course and mortality of patients.

Molecularly Targeted Lanthanide Nanoparticles for Cancer Theranostic Applications.

Injectable colloidal solutions of lanthanide oxides (nanoparticles between 10 and 100 nm in size) have demonstrated high biocompatibility and no toxicity when the nanoparticulate units are functionalized with specific biomolecules that molecularly target various proteins in the tumor microenvironment. Among the proteins successfully targeted by functionalized lanthanide nanoparticles are folic receptors, fibroblast activation protein (FAP), gastrin-releasing peptide receptor (GRP-R), prostate-specific membrane antigen (PSMA), and integrins associated with tumor neovasculature. Lutetium, samarium, europium, holmium, and terbium, either as lanthanide oxide nanoparticles or as nanoparticles doped with lanthanide ions, have demonstrated their theranostic potential through their ability to generate molecular images by magnetic resonance, nuclear, optical, or computed tomography imaging. Likewise, photodynamic therapy, targeted radiotherapy (neutron-activated nanoparticles), drug delivery guidance, and image-guided tumor therapy are some examples of their potential therapeutic applications. This review provides an overview of cancer theranostics based on lanthanide nanoparticles coated with specific peptides, ligands, and proteins targeting the tumor microenvironment.

Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review / Infección del sistema nervioso central por Streptococcus bovis en adultos: reporte de 4 casos y revisión de la literatura

Objectives: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. Methods: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. Results: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). Conclusions: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.(AU)

Introducción: Streptococcus bovis, una causa bien conocida de endocarditis asociada a cáncer colorrectal, es también una causa poco frecuente de infecciones del sistema nervioso central (SNC), incluyendo meningitis, abscesos cerebrales o empiema subdural. El objetivo de este estudio es describir las características clínicas, los antecedentes médicos y la asociación con la enfermedad intestinal en las infecciones por S. bovis en el SNC. Métodos: Describimos 4 infecciones por S. bovis en el SNC en nuestra Unidad y, a continuación, presentamos una revisión bibliográfica de los artículos publicados entre 1975-2021 en PubMed/MEDLINE. Resultados: Se encontraron 52 estudios con 65 casos; 5 se excluyeron por datos incompletos. En total se analizaron 64 casos incluyendo nuestros 4: 55 con meningitis y 9 con infecciones focales intracraneales. Ambas infecciones se asociaron con frecuencia a condiciones subyacentes (70,3%) como la inmunosupresión (32,8%) o el cáncer (10,9%). En 23 casos se identificó un biotipo, siendo el más frecuente el biotipo ii (69,6%), y dentro de ellos, S. pasteurianus. En el 60,9% de los casos se detectaron enfermedades intestinales, siendo las más frecuentes las neoplasias (41,0%) y la infestación por Strongyloides (30,8%). La mortalidad global fue del 17,1%, con una tasa mayor en la infección focal (44,4 frente a 12,7%; p=0,001). Conclusiones: Las infecciones del SNC debidas a S. bovis son poco frecuentes y la forma clínica más común es la meningitis. En comparación con las infecciones focales, la meningitis tiene un curso más agudo, está menos asociada a la endocarditis y tiene una menor mortalidad. La inmunosupresión y la enfermedad intestinal fueron frecuentes en ambas infecciones.(AU)

BCGitis with aortoiliac aneurysm involvement: Report of two cases and review of the literature.

BCGitis is a rare complication after intravesical administration of Bacillus Calmette-Guérin for high-grade superficial bladder cancer and carcinoma in situ. May cause vascular involvement. We present 2 cases and a review of the literature of the case reports pubished on the 10 years prior to April of 2022, when this proyect was finished, which described a case of aortoiliac mycotic aneurysm after receiving this treatment. Of the 51 cases included (49 revised and 2 original), 100% were men, 82% were older than 65 years. The median latency period was 15 months (IQR 18). The most frequent location was the abdominal aorta, rupture occurred in 45,1% of patients. The most frequent symptom was abdominal or lumbar pain (61%), followed by general syndrome (49%). In 39,2% cases, it was associated with retroperitoneal abscesess. Attributable mortality was 13,6%. BCGitis should be included in the differential diagnosis in patients who have received BCG therapy and present vascular involvement, even years after being treated.

Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review.

OBJECTIVES: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. METHODS: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. RESULTS: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). CONCLUSIONS: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.

Deep Learning Segmentation of Lower Extremities Radiographs for an Automatic Leg Length Discrepancy Measurement.

Leg length measurement is relevant for the early diagnostic and treatment of discrepancies as they are related with orthopedic and biomechanical changes. Simple radiology constitutes the gold standard on which radiologists perform manual lower limb measurements. It is a simple task but represents an inefficient use of their time, expertise and knowledge that could be spent in more complex labors. In this study, a pipeline for semantic bone segmentation in lower extremities radiographs is proposed. It uses a deep learning U-net model and performs an automatic measurement without consuming physicians' time. A total of 20 radiographs were used to test the methodology proposed obtaining a high overlap between manual and automatic masks with a Dice coefficient value of 0.963. The obtained Spearman's rank correlation coefficient between manual and automatic leg length measurements is statistically different from cero except for the angle of the left mechanical axis. Furthermore, there is no case in which the proposed automatic method makes an absolute error greater than 2 cm in the quantification of leg length discrepancies, being this value the degree of discrepancy from which medical treatment is required.Clinical Relevance- Leg length discrepancy measurements from X-ray images is of vital importance for proper treatment planning. This is a laborious task for radiologists that can be accelerated using deep learning techniques.

225Ac-iPSMA-RGD for Alpha-Therapy Dual Targeting of Stromal/Tumor Cell PSMA and Integrins.

Prostate-specific membrane antigens (PSMAs) are frequently overexpressed in both tumor stromal endothelial cells and malignant cells (stromal/tumor cells) of various cancers. The RGD (Arg-Gly-Asp) peptide sequence can specifically detect integrins involved in tumor angiogenesis. This study aimed to preclinically evaluate the cytotoxicity, biokinetics, dosimetry, and therapeutic efficacy of 225Ac-iPSMA-RGD to determine its potential as an improved radiopharmaceutical for alpha therapy compared with the 225Ac-iPSMA and 225Ac-RGD monomers. HEHA-HYNIC-iPSMA-RGD (iPSMA-RGD) was synthesized and characterized by FT-IR, UV-vis, and UPLC mass spectroscopy. The cytotoxicity of 225Ac-iPSMA-RGD was assessed in HCT116 colorectal cancer cells. Biodistribution, biokinetics, and therapeutic efficacy were evaluated in nude mice with induced HCT116 tumors. In vitro results showed increased DNA double-strand breaks through ROS generation, cell apoptosis, and death in HCT116 cells treated with 225Ac-iPSMA-RGD. The results also demonstrated in vivo cytotoxicity in cancer cells after treatment with 225Ac-iPSMA-RGD and biokinetic and dosimetric properties suitable for alpha therapy, delivering ablative radiation doses up to 237 Gy/3.7 kBq to HCT116 tumors in mice. Given the phenotype of HCT116 cancer cells, the results of this study warrant further dosimetric and clinical studies to determine the potential of 225Ac-iPSMA-RGD in the treatment of colorectal cancer.

99mTc-Labeled Cyclic Peptide Targeting PD-L1 as a Novel Nuclear Imaging Probe.

Recent cancer therapies have focused on reducing immune suppression in the tumor microenvironment to prevent cancer progression and metastasis. PD-1 is a checkpoint protein that stops the immune response and is expressed on immune T cells. Cancer cells express a PD-1 ligand (PD-L1) to bind to the T-cell surface and activate immunosuppressive pathways. This study aimed to design, synthesize, and evaluate a 99mTc-labeled PD-L1-targeting cyclic peptide inhibitor (99mTc-iPD-L1) as a novel SPECT radiopharmaceutical for PD-L1 expression imaging. AutoDock software (version 1.5) was used to perform molecular docking for affinity calculations. The chemical synthesis was based on the coupling reaction of 6-hydrazinylpyridine-3-carboxylic acid with a 14-amino-acid cyclic peptide. iPD-L1 was prepared for 99mTc labeling. Radio-HPLC was used to verify radiochemical purity. The stability of the radiopeptide in human serum was evaluated by HPLC. iPD-L1 specificity was assessed by SDS-PAGE. [99mTc]Tc-iPD-L1 cellular uptake in PD-L1-positive cancer cells (HCC827 and HCT116) and biodistribution in mice with induced tumors were also performed. One patient with advanced plantar malignant melanoma received [99mTc]Tc-iPD-L1. The iPD-L1 ligand (AutoDock affinity: -6.7 kcal/mol), characterized by UPLC mass, FT-IR, and UV-Vis spectroscopy, was obtained with a chemical purity of 97%. The [99mTc]Tc-iPD-L1 was prepared with a radiochemical purity of >90%. In vitro and in vivo analyses demonstrated [99mTc]Tc-iPD-L1 stability (>90% at 24 h) in human serum, specific recognition for PD-L1, high uptake by the tumor (6.98 ± 0.89% ID/g at 1 h), and rapid hepatobiliary and kidney elimination. [99mTc]Tc-iPD-L1 successfully detected PD-L1-positive lesions in a patient with plantar malignant melanoma. The results obtained in this study warrant further dosimetric and clinical studies to determine the sensitivity and specificity of [99mTc]Tc-iPD-L1/SPECT for PD-L1 expression imaging.

Design and Development of an Objective Evaluation System for a Web-Based Simulator for Trauma Management.

BACKGROUND: Trauma injuries are one of the main leading causes of death in the world. Training with guidelines and protocols is adequate to provide a fast and efficient treatment to patients that suffer a trauma injury. OBJECTIVES: This study aimed to evaluate deviations from a set protocol, a new set of metrics has been proposed and tested in a pilot study. METHODS: The participants were final-year students from the Universidad Autónoma de Madrid and first-year medical residents from the Hospital Universitario La Paz. They were asked to train four trauma scenarios with a web-based simulator for 2 weeks. A test was performed pre-training and another one post-training to evaluate the evolution of the treatment to those four trauma scenarios considering a predefined trauma protocol and based on the new set of metrics. The scenarios were pelvic and lower limb traumas in a hospital and in a prehospital setting, which allow them to learn and assess different trauma protocols. RESULTS: The results show that, in general, there is an improvement of the new metrics after training with the simulator. CONCLUSION: These new metrics provide comprehensive information for both trainers and trainees. For trainers, the evaluation of the simulation is automated and contains all relevant information to assess the performance of the trainee. And for trainees, it provides valuable real-time information that could support the trauma management learning process.

Localized Colonic Small-Cell Carcinoma with Pathological Complete Response after Neoadjuvant Cisplatin and Etoposide: A Case Report.

Extrapulmonary small-cell carcinoma (SCC) is a rare neoplasm that shares certain features with its pulmonary counterpart and occurs predominantly in the gastrointestinal tract (GIT). It is a high-grade and poorly differentiated neuroendocrine tumor, usually diagnosed in advanced stages, with a poor prognosis and few therapeutic options in that setting. This is a case report of a 77-year-old Spanish male patient with localized SCC of the colon, who presented a pathological complete response in the surgical specimen after neoadjuvant chemotherapy with cisplatin and etoposide. To date, 5 years after surgery, the patient remains without evidence of tumor recurrence. As clinical guidelines for the management of this entity are lacking, and therefore its management has not been standardized, an attempt to summarize the current evidence in the literature was made.

Synthesis and Evaluation of 177Lu-DOTA-PD-L1-i and 225Ac-HEHA-PD-L1-i as Potential Radiopharmaceuticals for Tumor Microenvironment-Targeted Radiotherapy.

Current cancer therapies focus on reducing immunosuppression and remodeling the tumor microenvironment to inhibit metastasis, cancer progression, and therapeutic resistance. Programmed death receptor 1 (PD-1) is expressed on immune T cells and is one of the so-called checkpoint proteins that can suppress or stop the immune response. To evade the immune system, cancer cells overexpress a PD-1 inhibitor protein (PD-L1), which binds to the surface of T cells to activate signaling pathways that induce immune suppression. This research aimed to synthesize PD-L1 inhibitory peptides (PD-L1-i) labeled with lutetium-177 (177Lu-DOTA-PD-L1-i) and actinium-225 (225Ac-HEHA-PD-L1-i) and to preclinically evaluate their potential as radiopharmaceuticals for targeted radiotherapy at the tumor microenvironment level. Using PD-L1-i peptide as starting material, conjugation with HEHA-benzene-SCN and DOTA-benzene-SCN was performed to yield DOTA-PD-L1-i and HEHA-PD-L1-I, which were characterized by FT-IR, UV-vis spectroscopy, and HPLC. After labeling the conjugates with 225Ac and 177Lu, cellular uptake in HCC827 cancer cells (PD-L1 positive), conjugate specificity evaluation by immunofluorescence, radiotracer effect on cell viability, biodistribution, biokinetics, and assessment of radiation absorbed dose in mice with in duced lung micrometastases were performed. 225Ac-HEHA-PD-L1-i and 177Lu-DOTA-PD-L1-i, obtained with radiochemical purities of 95 ± 3% and 98.5 ± 0.5%, respectively, showed in vitro and in vivo specific recognition for the PD-L1 protein in lung cancer cells and high uptake in HCC287 lung micrometastases (>30% ID). The biokinetic profiles of 177Lu-DOTA-PD-L1-i and 225Ac-DOTA-PD-L1-i showed rapid blood clearance with renal and hepatobiliary elimination and no accumulation in normal tissues. 225Ac-DOTA-PD-L1-i produced a radiation dose of 5.15 mGy/MBq to lung micrometastases. In the case of 177Lu-DOTA-PD-L1-i, the radiation dose delivered to the lung micrometastases was ten times (43 mGy/MBq) that delivered to the kidneys (4.20 mGy/MBq) and fifty times that delivered to the liver (0.85 mGy/MBq). Therefore, the radiotherapeutic PD-L1-i ligands of 225Ac and 177Lu developed in this research could be combined with immunotherapy to enhance the therapeutic effect in various types of cancer.

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses.

177Lu-iPSMA is a novel radioligand developed at ININ-Mexico with a high affinity for the PSMA protein heavily expressed in cancer cells of approximately 95% of patients with metastatic castration-resistant prostate cancer (mCRPC). 177Lu-DOTATOC is a patent-free radioligand, molecularly recognized by somatostatin receptors (SSTR-2) overexpressed in cancer cells of about 80% of patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). This translational research aimed to determine the efficacy and safety of 177Lu-iPSMA and 177Lu-DOTATOC developed as GMP pharmaceutical formulations for treating progressive and advanced mCRPC and NET. One hundred and forty-five patients with mCRPC and one hundred and eighty-seven subjects with progressive NET (83% GEP-NET and 17% other NET), treated with 177Lu-iPSMA and 177Lu-DOTATOC, respectively, were evaluated. Patients received a mean dose of 7.4 GBq per administration of 177Lu-iPSMA (range 1-5 administrations; 394 treatment doses) or 177Lu-DOTATOC (range 2-8 administrations; 511 treatment doses) at intervals of 1.5-2.5 months. Efficacy was assessed by SPECT/CT or PET/CT. Results were stratified by primary tumor origin and number of doses administered. Patients with mCRPC showed overall survival (OS) of 21.7 months with decreased radiotracer tumor uptake (SUV) and PSA level in 80% and 73% of patients, respectively. In addition, a significant reduction in pain (numerical scale from 10-7 to 3-1) was observed in 88% of patients with bone metastases between one and two weeks after the second injection. In the GEP-NET population, the median progression-free survival was 34.7 months, with an OS of >44.2 months. The treatments were well tolerated. Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of 177Lu-iPSMA and 177Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.

Modified Needleman-Wunsch algorithm for trauma management performance evaluation.

BACKGROUND: Trauma injuries are one of the leading causes of death in the world, representing approximately 8 % of all deaths. Therefore, trauma management training is of great importance and new training courses have arisen during the last decades. However, actual training courses do not typically analyze compliance with the protocols and guidelines available in the literature. Considering general trauma management guidelines such as the Advanced Trauma Life Support (ATLS) manual and the expertise of trauma specialists, a trauma management automated evaluation system has been designed in this paper. METHODS: A modification to the Needleman-Wunsch (NW) algorithm is developed, including all relevant aspects of trauma management to automatically evaluate how a trauma intervention has been implemented according to trauma protocols. This allows to consider more information with respect to the order of the actions taken and the type of actions performed than current evaluation methods, such as checklists or videos recorded in simulation. A web-based trauma simulator is used so that it can be used at any setting with internet connection. Final-year medical students and first- and second-year residents performed an experimental test, where a trauma score is obtained with the modified NW algorithm. This automatic score relates to how similar the actions are to trauma protocols. RESULTS: The results show the best combination of the scores used for the modified NW variables. This combination has an error, for the different case scenarios created, below 0.07 which verifies the values obtained. Additionally, trauma experts verified the results obtained showing a median difference of 0 between the protocol adherence evaluation using the algorithm and the one provided by the trauma experts. CONCLUSIONS: The best set of score values to apply to the modified NW algorithm show that the modified NW algorithm provides a successful objective measurement with respect to the protocol compliance.

Biokinetics, radiopharmacokinetics and estimation of the absorbed dose in healthy organs due to Technetium-99m transported in the core and on the surface of reconstituted high-density lipoprotein nanoparticles.

The development of rHDL-radionuclide theragnostic systems requires evaluation of the absorbed doses that would be produced in healthy tissues and organs at risk. Technetium-99m is the most widely used radionuclide for diagnostic imaging, therefore, the design of theragnostic reconstituted high density-lipoprotein (rHDL) nanosystems labeled with Technetium-99m offers multiple possibilities. OBJECTIVE: To determine the biokinetics, radiopharmacokinetics and estimate the absorbed doses induced in healthy organs by Technetium-99m transported in the core and on the surface of rHDL. METHODS: Biokinetic and radiopharmacokinetic models of rHDL/[99mTc]Tc-HYNIC-DA (Technetium-99m in the core) and [99mTc]Tc-HYNIC-rHDL (Technetium-99m on the surface) were calculated from their ex vivo biodistribution in healthy mice. Absorbed doses were estimated by the MIRD formalism using OLINDA/EXM and LMFIT softwares. RESULTS: rHDL/[99mTc]Tc-HYNIC-DA and [99mTc]Tc-HYNIC-rHDL show instantaneous absorption in kidney, lung, heart and pancreas, with slower absorption in spleen. rHDL/[99mTc]Tc-HYNIC-DA is absorbed more slowly in the intestine, while [99mTc]Tc-HYNIC-rHDL is absorbed more slowly in the liver. The main target organ for rHDL/[99mTc]Tc-HYNIC-DA, which is hydrophobic in nature, is the liver, whereas the kidney is for the more hydrophilic [99mTc]Tc-HYNIC-rHDL. Assuming that 925 MBq (25 mCi) of Technetium-99m, carried in the core or on the surface of rHDL, are administered, the maximum tolerated doses for the organs of greatest accumulation are not exceeded. CONCLUSION: Theragnostic systems based on 99mTc-labeled rHDL are safe from the dosimetric point of view. The dose estimates obtained can be used to adjust the 99mTc-activity to be administered in future clinical trials.