Desarrollo embriológico e importancia clínica de la membrana amniótica. Revisión narrativa de literatura

La membrana amniótica (MA), ubicada en el lado interno de la placenta fetal, ha sido objeto de múltiples investigaciones para intentar dilucidar su papel embriológico y su potencial celular terapéutico. Actualmente las limitaciones del estudio en fetos humanos hacen que parte de su funcionamiento sea una incógnita, sin embargo algunos estudios clínicos y básicos nos dan luz sobre su papel en la médica moderna. Se realizó una revisión bibliográfica de la literatura desde 1960 hasta 2022, empleando bases de datos como PubMed, SciELO y Scopus, siendo incluidos un total de 50 artículos y dos textos de embriología. El objetivo de esta revisión narrativa fue sintetizar la información sobre la angiogénesis y su importancia clínica. La información recopilada permitió evidenciar que las propiedades de curación de la piel del feto se deben a factores intrínsecos del feto, y a que las células epiteliales amnióticas humanas poseen una diferenciación similar a las células madre embrionarias, con la capacidad de diferenciación similar al de las células mesenquimales, resaltando su importancia clínica por sus características regenerativas. En conclusión, el desarrollo embrionario humano sigue siendo relativamente inexplicable, pero su conocimiento ha permitido grandes avances, que podrían ser útiles en terapias de regeneración, reparación de tejidos y órganos lesionados.

The amniotic membrane, located on the inner side of the fetal placenta, has been the subject of multiple investigations to try to elucidate its embryological role and its therapeutic cellular potential. Currently, the limitations of the study in human fetuses mean that part of its functioning is unknown, however, some clinical and basic studies shed light on its role in modern medicine. A bibliographic review of the literature was carried out from 1960 to 2022, using databases such as PubMed, SciELO and Scopus, including a total of 50 articles and two embryology texts. The objective of this narrative review was to synthesize information on angiogenesis and its clinical importance. The information collected made it possible to show that the healing properties of the fetal skin are due to intrinsic factors of the fetus, and that human amniotic epithelial cells have a differentiation similar to embryonic stem cells, with the differentiation capacity similar to that of mesenchymal cells, highlighting their clinical importance due to their regenerative characteristics. In conclusion, human embryonic development remains relatively inexplicable, but its knowledge has allowed great advances, which could be useful in regeneration therapies, repair of injured tissues and organs.

Use of complementary and alternative medicine by cancer patients in Colombia.

BACKGROUND: The use of complementary and alternative medicines (CAM) among cancer patients varies greatly. The available data suggest an increasing use of CAM over time and a higher prevalence in low- and middle-income countries. However, no reliable data are available from Latin America. Accordingly, we examined the prevalence of CAM use among cancer patients from six Colombian regions. METHODS: We conducted a survey on cancer patients attending comprehensive cancer centres in six capital cities from different regions. The survey was designed based on a literature review and information gathered through focus groups on CAM terminology in Colombia. Independent random samples of patients from two comprehensive cancer centres in every city were obtained. Patients 18 years and older with a histopathological diagnosis of cancer undergoing active treatment were eligible. The prevalence of CAM use is reported as a percentage with the corresponding confidence interval. CAM types are reported by region. The sociodemographic and clinical characteristics of CAM users and non-users were compared using Chi square and t tests. RESULTS: In total, 3117 patients were recruited. The average age 59.6 years old, and 62.8% were female. The prevalence of CAM use was 51.7%, and compared to non-users, CAM users were younger, more frequently women, affiliated with the health insurance plan for low-income populations and non-Catholic. We found no differences regarding the clinical stage or treatment modality, but CAM users reported more treatment-related side effects. The most frequent types of CAM were herbal products, specific foods and vitamins, and individually, soursop was the most frequently used product. Relevant variability between regions was observed regarding the prevalence and type of CAM used (range: 36.6% to 66.7%). The most frequent reason for using CAM was symptom management (30.5%), followed by curative purposes (19.5%). CONCLUSIONS: The prevalence of CAM use among cancer patients in Colombia is high in general, and variations between regions might be related to differences in cultural backgrounds and access to comprehensive cancer care. The most frequently used CAM products and practices have little scientific support, suggesting the need to enhance integrative oncology research in the country.

Use of an Autologous Heterogenous Skin Construct in the Treatment of Intractable Late-Effect Radiation Wounds: Case Series.

Background: Late-effect radiation-induced wounds represent a particularly difficult category of wounds to manage and treat. Fibrosis, impaired cellular activity, ischemia, and wound chronicity all work to impair healing, and this becomes more pronounced when defects are large or when avascular structures such as bone are exposed. Effective treatment options for this type of wound are limited. Thorough excision of irradiated tissue followed by distal pedicled or free flap closure is the most successful; however, this often requires multiple-stage surgeries and prolonged hospitalization and is associated with significant donor site morbidity. This is complicated further when wounds are large or in difficult locations, when surgery is not appropriate, or when there is limited access to surgeons with the appropriate experience/skill to perform such procedures. Methods: This case series describes the use of an autologous heterogenous skin construct (AHSC) made from a small full-thickness sample of the patient's healthy skin. Three patients with intractable late-effect radiation wounds were treated with AHSC. Case 1 describes an abdominal wound with tunneling of 7.5 cm to the pubic symphysis, which had been treated for known osteomyelitis, and a shallower full-thickness groin wound. Case 2 describes a right scapular wound with exposed bone, which had failed flap closure. Case 3 describes a right thigh wound in a patient who had been treated for sarcoma with extensive radiation therapy. This eventually resulted in an above-the-knee amputation, which failed to heal, and full exposure of the distal end of the resected femur. All wounds had been present for greater than 10 months. Results: Mean percent volume reduction was 83% (±2.7) at 3 weeks and 92.9% (±4.7) at 4 weeks. The tunneled abdominal wound decreased in depth from 7.5 cm to 1.2 cm in 3 weeks. Complete closure was achieved at 11 weeks for the abdominal and groin wounds (patient 1) and at 16 weeks for the thigh wound (patient 3). The scapular wound volume of patient 2 had decreased by 91.8% at week 4 but was not fully restored until week 21. Mean time to closure was 16.1 (±4.7) weeks. Conclusions: AHSC was effective in covering exposed bone, improving wound bed vascularity, filling in significant wound depth, and achieving complete wound closure with one application in patients with intractable late-effect radiation wounds.

Phenotypic expressions of the optic disc in primary open-angle glaucoma.

BACKGROUND: Which phenotypes are we able to recognize in the optic nerve of patients with primary open angle glaucoma? METHODS: Retrospective interventional case series. 885 eyes from 885 patients at an outpatient tertiary care centre who met specified criteria for POAG were included. Disc photographs were classified by three glaucoma specialists into the following phenotypes according to their predominant characteristics: (1) concentric rim thinning, (2) focal rim thinning, (3) acquired pit of the optic nerve (APON), (4) tilted, (5) extensive peripapillary atrophy (PPA), and (6) broad rim thinning. Demographic, medical, and ocular data were collected. Kruskal-Wallis was used as a non-parametric test and pairwise comparison was performed by using Wilcoxon rank sum test corrected. RESULTS: Phenotypic distribution was as follows: 398(45%) focal thinning, 153(18%) concentric thinning, 153(17%) broad thinning, 109(12%) tilted, 47(5%) extensive PPA and 25(3%) APON. Phenotypic traits of interest included a higher proportion of female patients with the focal thinning phenotype (p = 0.015); myopia (p = 0.000), Asian race (OR: 8.8, p = 0.000), and younger age (p = 0.000) were associated with the tilted phenotype; the concentric thinning patients had thicker RNFL (p = 0.000), higher MD (p = 0.008) and lower PSD (p = 0.043) than broad thinning, despite no difference in disc sizes (p = 0.849). The focal thinning group had a localized VF pattern with high PSD compared to concentric thinning (p = 0.005). CONCLUSION: We report six phenotypic classifications of POAG patients with demographic and ocular differences between phenotypes. Future refinement of phenotypes should allow enhanced identification of genetic associations and improved individualization of patient care.

Treatment of Stage 4 Pressure Injuries With Autologous Heterogenous Skin Construct: A Single-Center Retrospective Study.

Background: Pressure injuries (PIs) are a challenging problem in health care affecting 2.5 million people per year in the US, with 60,000 deaths directly attributed to PIs annually. Surgical closure is the treatment of choice for stage 3 and 4 PIs, but with complication rates of 59% to 73%, less invasive and more effective treatments are needed. Autologous heterogeneous skin construct (AHSC) is a novel autograft made from a small full-thickness harvest of healthy skin. This single-center retrospective cohort study sought to determine the effectiveness of AHSC in the treatment of recalcitrant stage 4 pressure injuries. Methods: All data were collected retrospectively. The primary efficacy outcome was complete wound closure. Secondary efficacy outcomes included percent area reduction, percent volume reduction, and coverage of exposed structures. Results: Seventeen patients with 22 wounds were treated with AHSC. Complete closure was achieved in 50% of patients in a mean time of 146 (SD ± 93) days, and the percent area and volume reductions were 69% and 81%, respectively. A 95% volume reduction was achieved in 68.2% of patients at a mean time of 106 (SD ± 83) days, and critical structures were fully covered in 95% of patients in a mean time of 33 (SD ± 19) days. After AHSC treatment, there was a mean decrease of 1.65 hospital admissions (P = .001), 20.92 hospital days (P < .001), and 2.36 operative procedures per year (P < 0.001). Conclusions: AHSC demonstrated the ability to cover exposed structures, restore wound volume, and achieve durable wound closure in chronic refractory stage 4 PIs with better closure and recurrence rates than current surgical and nonsurgical treatments. AHSC represents a minimally invasive alternative to reconstructive flap surgery that preserves future reconstructive options while minimizing donor-site morbidity and promoting improved patient health.

Endometrioma Within the Anterior Abdominal Wall Causing Cyclic Abdominal Pain.

Lesions from endometriosis contain endometrial glands and stroma outside the uterine cavity. The lesions occur in the pelvis but are also found in the bowel, diaphragm, and pleural cavity. Endometriosis within the extraperitoneal abdominal wall is rare, though, and usually within c-section scars (incidence is .03%-.5%). The typical triad includes: mass in the abdominal wall, cyclical pain, and history of previous abdominal surgery. We present the case of a 28-year-old female with a past history of cesarean section and obesity (BMI = 31) who presented with approximately 3 years of abdominal pain which was "waxing and waning" in severity depending on her menstrual cycle. Multiple doctors and US imaging did not reveal a diagnosis. During consultation, she had a palpable 3 cm mass several centimeters above and right of her abdominal incision. She underwent a CT showing an inflamed subcutaneous mass abutting her anterior rectus sheath. She underwent wide excision which confirmed the diagnosis of endometrioma. This case demonstrates the need for good history and physical exam skills, as well as proficiency in reviewing radiographic imaging. Due to habitus and pain, the physical exam was difficult. However, there was a firm mass upon deep palpation. Her initial imaging was "negative," but review of the images revealed only intraperitoneal views and further imaging revealed the mass. There must be high clinical suspicion for this disease because failure to remove all tissue (including the surrounding fibrosis and desmoplastic tissue) or biopsy can lead to spread of residual endometrial cells and recurrence.

Abordaje de la enfermedad de Behçet vulvar: comunicación de caso

La enfermedad de Behçet (EB) es un trastorno inflamatorio, multisistémico, recidivante y remitente de etiología desconocida. Una característica clave de la enfermedad es la ulceración orogenital que provoca una morbilidad considerable con gran impacto en la calidad de vida de los pacientes. Su manejo médico consiste en un esquema con colchicina, esteroides o inmunomoduladores. Comunicamos el caso de una paciente con lesiones genitales quien consultó en múltiples ocasiones, recibiendo manejo antibiótico e incluso quirúrgico, con respuesta refractaria a estas intervenciones. Posteriormente, por las características de las lesiones y el comportamiento clínico se sospechó enfermedad de Behçet y se instauró manejo médico con esteroides orales y curaciones con fitoestimulina. Hubo resolución de las úlceras genitales y posteriormente la paciente fue llevada a cirugía para corrección de las sinequias vulvares.

Behçet's disease (BD) is an inflammatory, multisystemic, relapsing-remitting disorder of unknown etiology. A key feature of the disease is orogenital ulceration that causes considerable morbidity with great impact on patient's quality of life. Its medical management consists of a scheme with colchicine, steroids or immunomodulators. We report the case of a patient with genital lesions who consulted on multiple occasions, receiving antibiotics and even surgical management, with refractory response to these interventions. Subsequently, due to the characteristics of the lesion and clinical behavior, Behçet's disease was suspected and medical management with oral steroids and cures with phytostimulin was initiated. The genital ulcers were resolved, and the patient was subsequently taken to surgery for correction of the vulvar synechiae.

A Neural Network for Automated Image Quality Assessment of Optic Disc Photographs.

This study describes the development of a convolutional neural network (CNN) for automated assessment of optic disc photograph quality. Using a code-free deep learning platform, a total of 2377 optic disc photographs were used to develop a deep CNN capable of determining optic disc photograph quality. Of these, 1002 were good-quality images, 609 were acceptable-quality, and 766 were poor-quality images. The dataset was split 80/10/10 into training, validation, and test sets and balanced for quality. A ternary classification model (good, acceptable, and poor quality) and a binary model (usable, unusable) were developed. In the ternary classification system, the model had an overall accuracy of 91% and an AUC of 0.98. The model had higher predictive accuracy for images of good (93%) and poor quality (96%) than for images of acceptable quality (91%). The binary model performed with an overall accuracy of 98% and an AUC of 0.99. When validated on 292 images not included in the original training/validation/test dataset, the model's accuracy was 85% on the three-class classification task and 97% on the binary classification task. The proposed system for automated image-quality assessment for optic disc photographs achieves high accuracy in both ternary and binary classification systems, and highlights the success achievable with a code-free platform. There is wide clinical and research potential for such a model, with potential applications ranging from integration into fundus camera software to provide immediate feedback to ophthalmic photographers, to prescreening large databases before their use in research.

Effects of cranioplasty in cerebral blood perfusion using quantification with 99m-Tc HMPAO SPECT-CT.

BACKGROUND AND PURPOSE: Syndrome of the trephined or sinking skin flap syndrome is an underdiagnosed condition of craniectomized patients that usually improves after cranioplasty. Among the pathophysiological theories proposed, the changes of cerebral blood perfusion (CBP) caused by cranial defects might have a role in the neurological deficiencies observed. We aim to assess the regional cortex changes in CBP after cranioplasty with Technetium 99m hexamethylpropylene-amine oxime (99mTc-HMPAO) SPECT-CT. METHODS: Twenty-eight craniectomized patients subject to cranioplasty were studied with 99mTc-HMPAO SPECT-CT in three different times, before cranioplasty, a week, and 3 months after. The images were processed with quantification software comparing CBP of 24 cortical areas with a reference area, and with a database of controls. A mixed effects model and T-Student were used. RESULTS: CBP increased significantly in both hemispheres after cranioplasty, either using ratio (ß = .019, p-value = .030 first postsurgical SPECT-CT and ß = .021, p-value = .015 in the second study, vs. presurgical) or Z-score (ß = .220, p-value = .026 and ß = .279, p-value = .005, respectively). Nine areas of the damaged side had a significant lower CBP ratio and Z-score than the undamaged. Posterior cingulate showed an increased CBP ratio (p-value = .034) and Z-score (p-value = .028) in the first postsurgical SPECT-CT. These posterior cingulate changes represent a 4.83% increase in ratio and 91.04% in Z-Score (p-value = .035 and .040, respectively). CONCLUSION: CBP changes significantly in specific cortical areas after cranioplasty. Posterior cingulate changes might explain some improvements in attention impairments. SPECT-CT could be a useful tool to assess CBP changes in these patients and might be helpful in their clinical management.

The hand grip training device: A new therapeutic option in arteriovenous fistula maturation.

INTRODUCTION: Postoperative exercise improves arteriovenous fistula maturation for hemodialysis. However, scarce evidence exists about hand grip device on fistula maturation process. OBJECTIVE: To evaluate the efficacy of a hand grip training program on arteriovenous fistula maturation in population with Chronic Kidney Disease 5-5D. METHODOLOGY: Prospective study (15 months). Patients were randomized to handgrip (HG) or control group (CG) postoperatively. HG performed a training program using a hand grip device. CG received conventional care. Upper limb muscle strength (ULMS), Duplex ultrasonography, and clinical arteriovenous fistula maturation were assessed at 4 and 8 weeks postoperatively. RESULTS: At 8 weeks after fistula creation, upper limb muscle strength was increased only in the handgrip group (from 18 ± 6 to 23 ± 9 kg, p = 0.023). Clinical maturation was significantly greater in handgrip group versus control group, both at 4 weeks after intervention (62% vs 23%, p = 0.004) and at 8 weeks (65% vs 27%, p = 0.004). Similarly, the Doppler ultrasonography maturation rates were significantly greater in the HG, both at 4 weeks (HG: 84% vs CG: 47%; p = 0.004) and at 8 weeks (HG: 89% vs CG: 50%; p = 0.002). CONCLUSIONS: The hand grip is a useful and safety training device to improve the arteriovenous fistula maturation. This device results a new therapeutic option for maturation in arteriovenous fistula, particularly in distal arteriovenous fistula. Further studies are required to support these results.

Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

PURPOSE: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies. PATIENTS AND METHODS: Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non-small-cell lung cancer with programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1)-directed monotherapy or in combination with chemotherapy. CtDNA levels were measured using different ctDNA assays across the studies. Maximum variant allele frequencies were calculated using all somatic tumor-derived variants in each unique patient sample to correlate ctDNA changes with overall survival (OS) and progression-free survival (PFS). RESULTS: We observed strong associations between reductions in ctDNA levels from on-treatment liquid biopsies with improved OS (OS; hazard ratio, 2.28; 95% CI, 1.62 to 3.20; P < .001) and PFS (PFS; hazard ratio 1.76; 95% CI, 1.31 to 2.36; P < .001). Changes in the maximum variant allele frequencies ctDNA values showed strong association across different outcomes. CONCLUSION: In this pooled analysis of five independent clinical trials, consistent and robust associations between reductions in ctDNA and outcomes were found across multiple end points assessed in patients with non-small-cell lung cancer treated with an ICI. Additional tumor types, stages, and drug classes should be included in future analyses to further validate this. CtDNA may serve as an important tool in clinical development and an early indicator of treatment benefit.

Patient, Family Member and Physician Perspectives and Experiences with AML Treatment Decision-Making.

INTRODUCTION: Treatment decisions in older adults with acute myeloid leukemia (AML) are challenging, particularly for those who are not candidates for intensive chemotherapy (IC), and the trade-offs patients, their families and physicians consider when choosing a treatment option are not well understood. This qualitative research explored the value of extending survival and the treatment decision-making process from a multi-stakeholder perspective. METHODS: Overall, 28 patients with AML (≥ 65 years old, unsuitable for IC), 25 of their relatives and 10 independent physicians from the US, UK and Canada took part in one-on-one, 60-minute qualitative interviews. RESULTS: Across all stakeholders, improved health-related quality of life (HRQoL), extended survival and relief of AML symptoms were recognized as most important in AML treatment decision-making. However, extending survival in 'good health' was more important than extending survival alone, particularly because of the extra time it gives patients and their relatives together, and allows patients to achieve important goals. Patients' limited understanding of available treatment options, paired with incorrect perceptions of treatment side effects, impacted their involvement in the treatment decision-making process. Patients and physicians perceived physicians to have the most influence in the decision-making process despite their priorities not always aligning. CONCLUSION: These findings illustrate the importance of having structured discussions which explicitly assess patients' goals and their understanding and expectations of treatments and also the need for patient friendly resources about the lived experience of AML and available treatment options. These measures will help to ensure that patients are fully involved in the shared decision-making process.

Dolor lumbar en el embarazo, aspectos fisiopatológicos y tratamiento / Low back pain in pregnancy, pathophysiological aspects and treatment

INTRODUCCIÓN: El dolor lumbar es una condición de alta prevalencia en la población general. La gestación genera cambios fisiológicos que favorecen la aparición de síntomas dolorosos que pueden comprometer la calidad de vida. MÉTODO: Revisión de la literatura con términos MeSH en inglés y español en las bases de datos Embase, PubMed, Lilacs, Sage, Google Academics y Scielo desde el año 1994 hasta el año 2021. Se encontraron 74 artículos y fueron seleccionados 50, basados en su impacto clínico. RESULTADOS: El dolor lumbar afecta a más del 50% de las mujeres embarazadas. Existen antecedentes gineco-obstétricos que pueden intervenirse para disminuir el riego o la intensidad de los síntomas. El diagnóstico es clínico, pero puede asociarse a imágenes diagnósticas cuando se sospechan condiciones de riesgo. El tratamiento se basa en intervenciones no farmacológicas como ejercicio y terapia física, pero pueden utilizarse algunos medicamentos e intervenciones en dolor según su riesgo-beneficio materno y fetal. CONCLUSIONES: El dolor lumbar en el embarazo es muy frecuente y debe ser conocido, diagnosticado y tratado por los profesionales de la salud que atienden esta población, dentro de un equipo multidisciplinario de tratamiento.

INTRODUCTION: Low back pain is a condition of high prevalence in the general population. Gestation generates physiological changes that favor the appearance of painful symptoms that can compromise the quality of life. METHOD: Review of the literature with MeSH terms in English and Spanish in the databases Embase, PubMed, Lilacs, Sage, Google Academics and Scielo from the year 1994 to the year 2021. Seventy-four articles were found and 50 were selected based on their clinical impact. RESULTS: Low back pain affects more than 50% of pregnant women. There are gyneco-obstetric antecedents that can be intervened to reduce the risk or intensity of symptoms. The diagnosis of this entity is clinical, but it can be associated with diagnostic imaging when risk conditions are suspected. Treatment is based on non-pharmacological interventions such as exercise and physical therapy, but some medications and pain interventions can be used according to their risk of maternal and fetal benefit. CONCLUSIONS: Low back pain in pregnancy is very frequent, it should be known, diagnosed, and treated by health professionals who care for this population, based on a multidisciplinary treatment team.

Homologous Recombination Deficiency: Concepts, Definitions, and Assays.

BACKGROUND: Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting. METHODS: Friends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status. RESULTS: This publication provides findings from the group's discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community. CONCLUSION: Overall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.

Riesgo-beneficio de la retirada de estatinas en cuidados paliativos: revisión sistemática de la literatura / Risks and benefits of statin deprescription in palliative care: a systemic review of the literature

Introducción: El uso de estatinas en pacientes con enfermedad terminal avanzada no queda claro; el tiempo para obtener un beneficio es superior a la supervivencia, a los efectos adversos e interacciones farmacológicas. El objetivo es buscar evidencia científica del riesgo-beneficio en la retirada de estatinas en pacientes con enfermedad terminal avanzada. Metodología: Revisión sistemática bibliográfica de artículos en inglés y español publicados entre 2013 y 2018. Bases de datos: Pubmed, Scopus, Cochrane, Google académico, Cercatot de la web de la Biblioteca de la Universidad de Lleida. Parámetros analizados: tipo de estudio, tamaño de muestra, esperanza de vida, resultados más significativos y posibles limitaciones. Selección de artículos mediante la lectura del título y/o resumen, posterior lectura completa del texto. Resultados: Encontramos 224 artículos, 13 cumplen criterios. Los beneficios de estatinas en prevención primaria se observan entre 6 meses y 3 años. Presentan mayor susceptibilidad a efectos adversos personas con edad avanzada, caquexia o fragilidad. Los efectos adversos principales fueron: gastrointestinales (8 %), dolores musculoesqueléticos (mayor al 7 %). Las miopatías fueron más frecuentes en mujeres y en personas con niveles de vitamina D bajos. Las interacciones principales fueron con amlodipino, fluconazol o ketoconazol, warfarina, verapamilo o eritromicina. Mejor calidad de vida percibida en el grupo que descontinúa estatinas. La desprescripción ocurre habitualmente horas o días antes del fallecimiento. Conclusiones: La intervención paliativa precoz al retirar las estatinas cuando estas ya no ofrezcan un beneficio podría ofrecer beneficios como evitar efectos adversos e interacciones y mejorar la calidad de vida. Sería útil la estandarización de criterios. (AU)

Introduction: The use of statins in patients with advanced terminal disease is unclear: the time needed to obtain benefits is greater than survival, and adverse effects as well as pharmacological interactions may occur. The objective was to find scientific information regarding the risks and benefits of statin deprescription in patients with limited prognosis. Methodology: A systematic review of the literature in English and Spanish published between 2013 through 2018. Search: PubMed, Scopus, Cochrane, Google Scholar, Cercatot (University of Lleida web services). Data analyzed: type of study, population size, life expectancy, notable results, and possible limitations. The selection of articles was done by reading the title and/or abstract; the whole paper was read subsequently. Results: We found 224 articles, 13 met the criteria. The benefits of statins in primary prevention are observed between 6 months and 3 years. An increased susceptibility to side effects was seen in the elderly, cachectic, or frail patients. Major side effects included: gastrointestinal events (8%), and musculoskeletal pain (above 7%). Myopathies were more common in women and in people with low vitamin D levels. Most common interactions occurred with amlodipine, fluconazole or ketoconazole, warfarin, verapamil or erythromycin. A better quality of life was perceived in the group that discontinued statins. Deprescription usually occurs hours or days before death. Conclusions: In early palliative intervention the withdrawal of statins when they no longer offer any benefits could benefit our patients by avoiding adverse effects and interactions, thus improving quality of life. A standardization of criteria would be useful. (AU)

Continuing to Broaden Eligibility Criteria to Make Clinical Trials More Representative and Inclusive: ASCO-Friends of Cancer Research Joint Research Statement.

PURPOSE: Restrictive clinical trial eligibility criteria (EC) limit the number of patients who can enroll and potentially benefit from protocol-driven, investigational treatment plans and reduce the generalizability of trial results to the broader population. Following publication of expert stakeholder recommendations for broadening EC in 2017, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) convened working groups to produce additional recommendations and analyze the potential impact on clinical trials using real-world data. EXPERIMENTAL DESIGN: Multistakeholder working groups were appointed by an ASCO-Friends leadership group to propose recommendations for more inclusive EC related to: washout periods, concomitant medications, prior therapies, laboratory reference ranges and test intervals, and performance status. RESULTS: The four working groups, ASCO Board of Directors, and Friends leadership support the recommendations included in this statement to modernize EC related to washout periods, concomitant medications, prior therapies, laboratory references ranges and test intervals, and performance status to make trial populations more inclusive and representative of cancer patient populations. CONCLUSIONS: Implementation of the recommendations is intended to result in greater ease of determining patient eligibility. Increased opportunities for patient participation in research will help address longstanding underrepresentation of certain groups in clinical trials and produce evidence that is more informative for a broader patient population. More patients eligible will also likely speed clinical trial accrual.See related commentary by Giantonio, p. 2369.

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Prior Therapies Work Group.

PURPOSE: Restrictive eligibility criteria induce differences between clinical trial and "real-world" treatment populations. Restrictions based on prior therapies are common; minimizing them when appropriate may increase patient participation in clinical trials. EXPERIMENTAL DESIGN: A multi-stakeholder working group developed a conceptual framework to guide evaluation of prevailing practices with respect to using prior treatment as selection criteria for clinical trials. The working group made recommendations to minimize restrictions based on prior therapies within the boundaries of scientific validity, patient centeredness, distributive justice, and beneficence. RECOMMENDATIONS: (i) Patients are eligible for clinical trials regardless of the number or type of prior therapies and without requiring a specific therapy prior to enrollment unless a scientific or clinically based rationale is provided as justification. (ii) Prior therapy (either limits on number and type of prior therapies or requirements for specific therapies before enrollment) could be used to determine eligibility in the following cases: a) the agents being studied target a specific mechanism or pathway that could potentially interact with a prior therapy; b) the study design requires that all patients begin protocol-specified treatment at the same point in the disease trajectory; and c) in randomized clinical studies, if the therapy in the control arm is not appropriate for the patient due to previous therapies received. (iii) Trial designers should consider conducting evaluation separately from the primary endpoint analysis for participants who have received prior therapies. CONCLUSIONS: Clinical trial sponsors and regulators should thoughtfully reexamine the use of prior therapy exposure as selection criteria to maximize clinical trial participation.See related commentary by Giantonio, p. 2369.

Implementation Models of Compassionate Communities and Compassionate Cities at the End of Life: A Systematic Review.

In the last decade, we have seen a growth of Compassionate Communities and Cities (CCC) at the end of life. There has been an evolution of organizations that help construct Community-Based Palliative Care programs. The objective is to analyze the implementation, methodology and effectiveness of the CCC models at the end of life. We conducted a systematic review following PRISMA ScR Guideline. The protocol was registered on PROSPERO (CRD42017068501). Five databases (MEDLINE, EMBASE, Web of Science, CINAHL and Google Scholar) were searched for studies (from 2000 to 2018) using set eligibility criteria. Three reviewers screened full-texts articles and extracted study data. Outcomes were filled in a registration form which included a narrative synthesis of each article. We screened 1975 records. We retrieved 112 articles and included 31 articles for the final analysis: 17 descriptive studies, 4 interventions studies, 4 reviews and 6 qualitative studies. A total of 11 studies regard the development models of CCC at the end of life, 15 studies were about evaluation of compassionate communities' programs and 5 studies were about protocols for the development of CCC programs. There is poor evidence of the implementation and evaluation models of CCC at the end of life. There is little and low-/very low-quality evidence about CCC development and assessment models. We found no data published on care intervention in advance disease and end of life. A global model for the development and evaluation of CCC at the end of life seems to be necessary.

A National Assessment of Diagnostic Test Use for Patients with Advanced NSCLC and Factors Influencing Physician Decision-Making.

BACKGROUND: Diagnostic tests, including US Food and Drug Administration (FDA)-approved tests and laboratory-developed tests, are frequently used to guide care for patients with cancer, and, recently, have been the subject of several policy discussions and insurance coverage determinations. As the use of diagnostic testing has evolved, stakeholders have raised questions about the lack of standardized test performance metrics and the risk this poses to patients. OBJECTIVES: To describe the use of diagnostic testing for patients with advanced non-small-cell lung cancer (NSCLC), to analyze the utilization of FDA-approved versus laboratory-developed diagnostic tests, and to evaluate the impact of existing regulatory and coverage frameworks on diagnostic test ordering and physician treatment decision-making for patients with advanced NSCLC. METHODS: We conducted a 2-part study consisting of an online survey and patient chart review from March 1, 2019, to March 25, 2019, of physicians managing patients with advanced NSCLC. Respondents qualified for this study if they managed at least 5 patients with advanced NSCLC per month and had diagnosed at least 1 patient with advanced NSCLC in the 12 months before the survey. A total of 150 physicians completed the survey; before completing the survey, they were instructed to review between 4 and 8 charts of patients with stage IV NSCLC from their list of active patients. RESULTS: A total of 150 practicing oncologists who manage patients with advanced NSCLC responded to the survey and reviewed a total of 815 patient charts. Of these 815 patients, 812 (99.6%) were tested for at least 1 biomarker, including 73% of patients who were tested for EGFR, 70% tested for ALK, 58% tested for BRAF V600E, and 38% of patients tested for ROS1, by FDA-approved diagnostic tests. In all, 185 (83%) patients who tested positive for EGFR and 60 (83%) patients who tested positive for ALK received an FDA-approved targeted therapy for their biomarker. A total of 98 (65%) physicians responded that the patient's insurance coverage factored into their decision to order diagnostic tests and 69 (45%) physicians responded that cost or the patient's insurance coverage could influence them not to prescribe an indicated targeted therapy. CONCLUSION: The survey results indicate that diagnostic testing has become routine in the treatment of patients with advanced NSCLC, the use of FDA-approved diagnostic tests has increased, and insurance coverage and cost influence patient access to diagnostic testing as well as to targeted treatment options.