Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients.

PURPOSE: Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. METHODS: Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. RESULTS: Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45 years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. CONCLUSION: In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was even lower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

MicroRNAs and Child Neuropsychiatric Disorders: A Brief Review.

MicroRNAs (miRNAs) are short, endogenous, noncoding RNAs that regulate gene expression through posttranscriptional mechanisms via degradation or inhibition of specific mRNAs targets. In recent years, abundant studies have illustrated the relevance of miRNAs in human psychopathology. In this current review, neuropsychiatric disorders with moderate to high prevalence among children and adolescents such as Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, Dyslexia, Epilepsy, Schizophrenia and Tourette Syndrome were discussed focusing on the functional consequence of altered miRNA expression during the development of such diseases. The insight about the roles that miRNAs play in central nervous systems development such as cell proliferation and differentiation, synaptogenesis, synaptic plasticity, and apoptosis might be the key to explicate novel biomarkers for diagnosis and prognosis of these disorders, as well as the finding of new targets for drug development for therapeutic approaches.

Effect of dissolved oxygen and temperature on macromolecular composition and PHB storage of activated sludge.

The macromolecular composition of activated sludge (lipids, intracellular proteins and intracellular polysaccharides) was studied together with its capacity to store macromolecules such as polyhydroxybutyrate (PHB) in a conventional activated sludge system fed with synthetic sewage water at an organic load rate of 1.0 kg COD/(m(3)·d), varying the dissolved oxygen (DO) and temperature. Six DO concentrations (0.8, 1.0, 1.5, 2.0, 2.5 and 8 mg/L) were studied at 20°C with a sludge retention time (SRT) of 6 days. In addition, four temperatures (10ºC, 15ºC, 20ºC and 30ºC) were assessed at constant DO (2 mg/L) with 2 days SRT in a second experimental run. The highest lipid content in the activated sludge was 95.6 mg/g VSS, obtained at 30°C, 2 mg/L of DO and a SRT of 2 days. The highest content of intracellular proteins in the activated sludge was 87.8 mg/g VSS, obtained at 20°C, 8 mg/L of DO and a SRT of 6 days. The highest content of intracellular polysaccharides in the activated sludge was 76.6 mg/g VSS, which was achieved at 20°C, a SRT of 6 days and a wide range of DO. The activated sludge PHB storage was very low for all the conditions studied.

Evaluation of the psychometric properties of the family adaptability and cohesion scale (FACES III) through item response theory models in students from Chile and Colombia.

BACKGROUND: A psychometric study of the Family Adaptability and Cohesion Scale (FACES III) has been conducted in Spanish-speaking countries from the perspective of the classical test theory. However, this approach has limitations that affect the psychometric understanding of this scale. OBJECTIVE: Accordingly, this study used the item response theory to investigate the psychometric performance of the items. Furthermore, it evaluated the differential performance of the items for Colombia and Chile. METHOD: For this purpose, 518 health science students from both countries participated. Confirmatory Factor Analysis was used. RESULTS: The study results revealed that the cohesion and adaptability items presented adequate discrimination and difficulty indices. In addition, items 5, 8, 13, 17, and 19 of cohesion indicated differential functioning between students from both countries, with Chilean students exhibiting a greater discriminatory power. Further, the Colombian group exhibited a greater discriminatory power for item 18 of adaptability. CONCLUSIONS: The study concluded that the items of FACES III indicated adequate psychometric performance in terms of their discriminative capacity and difficulty in Chile and Colombia.

[Effects of postural control upon anti-saccade error rate in older people]. / Efectos del control postural en la tasa de error anti-sacádico en personas mayores.

BACKGROUND: The anti-saccadic (AS) error-rate is used to diagnose neurological disorders. The natural aging process could generate difficulty in carrying out parallel neural processes of conscious motor inhibition and eye movement. Therefore, if balance control is imposed on an elderly person in biped positions during an AS movement, an increase in the AS error-rate is expected. OBJECTIVE: To study the effects of postural control on the AS error-rate in older people. METHODS: An intra and intergroup comparison was made of AS error-rate in an experimental group of older people (PM) and another control group of young people (PJ). For this, blocks of AS and pro-saccadic movements (control) were used randomly in four different postures: (1)sitting (SENT), (2)standing normally (NORMAL), (3)feet together (REDUC), and (4)feet in line (TANDEM). RESULTS: The PM group, compared to the PJ group, showed a progressive increase in the AS error-rate from the sitting position to all standing positions, with the maximum AS error-rate in more complex vertical postures. In contrast, the PJ group did not present significative variability of this AS error-rate in all positions. CONCLUSIONS: It is confirmed that the aging process is associated with an increase in the AS error-rate. This study reveals for the first time a significant increase in the AS error-rate when control of body balance is required for PM, implying a decrease in the multiple processing capacity in PM for the execution of complex and parallel tasks.

Delivering Palliative and Supportive Care for Older Adults with Cancer: Interactions between Palliative Medicine and Geriatrics.

The world's population is aging rapidly, with projections indicating that by 2050 one in six people will be aged ≥65 years. As a result, the number of cancer cases in older people is expected to increase significantly. Palliative care is an essential component of cancer care with a direct impact on quality of life. However, older adults with cancer often suffer from multiple comorbidities, cognitive impairment, and frailty, posing unique challenges in the delivery of palliative care. The complex healthcare needs of older patients with cancer therefore require a comprehensive assessment, including a geriatric evaluation. Collaboration between geriatrics and palliative care can offer a solution to the challenges faced by older people with cancer, since this is a population with overlapping concerns for both disciplines. This review highlights the importance of palliative care for older adults with cancer and the benefits of a multidisciplinary approach. It also addresses the coordination of palliative care and geriatrics for specific symptom management and decision making.

[A comparative study for adenosine deaminase and anti-antigen A-60 antibodies detection for the diagnosis of tuberculous meningitis]. / Comparación de adenosina deaminasa y detección de anticuerpos anti-antígeno A60 para el diagnóstico de meningitis tuberculosa.

BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of rapid and accurate diagnostic tools. We evaluated the immunological response to Mycobacterium tuberculosis anti-A60 antibodies in cerebrospinal fluid (CSF) in comparison to adenosine deaminase (ADA) determination, for the diagnosis of TBM. METHODS: A total of 63 CSF samples were analyzed by indirect ELISA for the detection of anti- A60 IgG, IgM and IgA. These include samples from 17 patients with confirmed TBM and 46 control patients with other infections. RESULTS: The mean individual anti-A60 IgM, IgG and IgA CSF antibody titers were significantly higher in TBM in comparison with control groups (p < 0.01). The best discriminatory CSF antibody for confirming TBM diagnosis was IgM, with an area under the receiver operating characteristic curve of 0.928 (95%CI 0.834-0.978), compared to 0.863 (95% CI: 0.752-0.936) for ADA testing (p = NS). The sensitivity of anti- A60 IgM CSF antibody titers (cutoff > 0.06 U/ml) was 94.1% compared to 88.2% for ADA (cutoff > 6.2 U/ml), p = NS. Both anti A60 IgM and ADA showed the same moderate specificity (80.4%). Two cases of TBM were correctly identified by anti-A60 IgM but missed by ADA. CONCLUSION: The ELISA test for anti-antigen A60 antibodies (IgM) is a rapid and sensitive tool for the rapid diagnosis of TBM that can be a complement to ALDA determination. The specificity of both tests is still a limitation in TBM diagnosis.

[Effects of physical exercise on sleep quality, insomnia, and daytime sleepiness in the elderly. A literature review]. / Efectos del ejercicio físico sobre la calidad del sueño, insomnio y somnolencia diurna en personas mayores. Revisión de la literatura.

The ageing process alters the stages of sleep, and the elderly that have this problem tend to be prescribed pharmacological treatment. This has long term side effects and results in increased health costs. On the other hand, frequent or regular physical exercise could be an overall superior alternative, due to its multifactorial effects. It is also less expensive, thus more affordable and accessible. Furthermore, these benefits could be extrapolated to the quality of sleep. Taking this into account the purpose of this paper is to establish the proper amount of physical exercise using the FITT (frequency, intensity, time, type of exercise) principle, and its effect on the quality of sleep, insomnia, and daytime sleepiness in the elderly. This could lead us to a paradigm shift in the treatment of sleep disorders, and also may constitute an alternative method for treating the elderly.

AIDS presenting as radial bone tuberculosis and pyogenic methicillin-sensitive Staphylococcus aureus osteomyelitis.

Osteomyelitis is a rare initial presentation of HIV. We report a case of a 25-year-old, apparently well man presenting with a traumatic, pathological fracture of the right radius. He had a 2-week history of low-grade fever, swelling and purulent discharge of the radial aspect of his right forearm. Osteomyelitis, secondary bacteraemia and pneumonia were clues that led physicians to test for HIV. Multiple debridement, sequestrectomy and vacuum-assisted closure were done. Tissue cultures revealed Mycobacterium tuberculosis (TB) and methicillin-sensitive Staphylococcus aureus He was treated successfully with 6 weeks of culture-guided intravenous oxacillin, staphylococcal decontamination and first-line anti-TB regimen (rifampicin, isoniazid, ethambutol, pyrazinamide). Antiretroviral agents were started thereafter. Successful infection control and preservation of limb functionality was achieved with a multidisciplinary team approach. To our knowledge this is the first reported case of an adult patient with HIV presenting with tuberculous and pyogenic osteomyelitis of the radial bone.

Comparison of Muscle Energy Technique, Myofascial Release, and Combined Techniques for Glenohumeral Internal-Rotation Deficit. An Interventional Study

SUMMARY: This study aimed to determine the benefits of a combined technique of muscle energy with and myofascial release more effective than using each in isolation in glenohumeral internal rotator deficits. An interventional study was designed for this study. Thirty-eight patients were diagnosed with painful shoulder syndrome. Patients were randomly allocated into 4 groups where Group A was treated with combined muscle energy and myofascial release; Group B with muscle energy technique; Group C with myofascial release and Group D used as control. The evaluation of the passive joint range of the glenohumeral internal rotation and sociodemographic data for each of the groups were measured, before and after interventions. Despite the use of myofascial release and muscle energy techniques being significantly beneficial in their respective groups, when both were combined; it outcomes were highly successful. A combination therapy treatment applied with the Muscle Energy and Myofascial Release Techniques in patients with painful shoulder syndrome will be more effective in increasing the range of motion of the glenohumeral internal rotation joint than any of the techniques applied individually.

Este estudio tuvo como objetivo determinar los beneficios de una técnica combinada de energía muscular con liberación miofascial más efectiva que usar cada una de manera aislada en los déficits de los músculos rotadores internos glenohumerales. Para este estudio se diseñó un protocolo de intervención. En 38 pacientes se diagnosticó síndrome de hombro doloroso. Los pacientes fueron asignados aleatoriamente a 4 grupos; el grupo A fue tratado con energía muscular combinada y liberación miofascial; Grupo B con técnica de energía muscular; Grupo C con liberación miofascial y Grupo D utilizado como control. Se midió la evaluación del rango articular pasivo de la rotación interna de la articulación glenohumeral y datos sociodemográficos de cada uno de los grupos, antes y después de las intervenciones. A pesar de que el uso de técnicas de liberación miofascial y energía muscular resultó significativamente beneficioso en sus respectivos grupos, cuando ambas se combinaron; Sus resultados fueron muy exitosos. Un tratamiento de terapia combinada aplicado con las Técnicas de Energía Muscular y Liberación Miofascial en pacientes con síndrome de hombro doloroso será más efectivo para aumentar el rango de movimiento de la articulación de rotación interna glenohumeral que cualquiera de las técnicas aplicadas individualmente.

Insulin resistance and Alzheimer's disease: molecular links & clinical implications.

Hyperinsulinemia as well as type II diabetes mellitus are among the risk factors for Alzheimer's disease (AD). However, the molecular and cellular basis that link insulin resistance disorders and diabetes with AD are far from clear. Here, we discuss the potential molecular mechanisms that may explain the participation of these metabolic disorders in the pathogenesis of AD. The human brain uses glucose as a primary fuel; insulin secreted by the pancreas cross the blood-brain barrier (BBB), reaching neurons and glial cells, and exerts a region-specific effect on glucose metabolism. Glucose homeostasis is critical for energy generation, neuronal maintenance, neurogenesis, neurotransmitter regulation, cell survival and synaptic plasticity. It also plays a key role in cognitive function. In an insulin resistance condition, there is a reduced sensitivity to insulin resulting in hyperinsulinemia; this condition persists for several years before becoming full-blown diabetes. Toxic levels of insulin negatively influence neuronal function and survival, and elevation of peripheral insulin concentration acutely increases its cerebrospinal fluid (CSF) concentration. Peripheral hyperinsulinemia correlates with an abnormal removal of the amyloid beta peptide (Abeta) and an increase of tau hyperphosphorylation as a result of augmented cdk5 and GSK3beta activities. This leads to cellular cascades that trigger a neurodegenerative phenotype and decline in cognitive function. Chronic peripheral hyperinsulinemia results in a reduction of insulin transport across the BBB and a reduced insulin signaling in brain, altering all of insulin's actions, including its anti-apoptotic effect. However, the increase in brain insulin levels resulting from its peripheral administration at optimal doses has shown a cognition-enhancing effect in patient with AD. Some drugs utilized in type II diabetes mellitus reduce cognitive impairment associated with AD. The link between insulin resistance and neurodegeneration and AD, and the possible therapeutic targets in preventing the insulin-resistance disorders are analyzed.

Efectos de un Programa de Ejercicios y Educación en Dolor mediante Tele-rehabilitación en la Calidad de Vida de Mujeres Jóvenes con Dismenorrea Primaria / Effects of an Exercise and Pain Education Program via Telerehabilitation on the Quality of Life of Young Women with Primary Dysmenorrhea

Introducción. La dismenorrea primaria afecta la calidad de vida de mujeres jóvenes. Este estudio investiga los efectos de un protocolo de ejercicios y educación en dolor mediante telerehabilitación. Objetivo. Determinar los efectos de un protocolo de ejercicios y educación en dolor y su impacto en la calidad de vida mediante tele-rehabilitación en mujeres jóvenes con dismenorrea primaria. Métodos. Se realizó un estudio experimental pre y post test con un grupo control, utilizando tele-rehabilitación. Participaron 21 mujeres jóvenes con dismenorrea primaria, asignadas aleatoriamente a dos grupos: el grupo experimental (10 mujeres) y el grupo control (11 mujeres). Se utilizaron cuestionarios específicos de calidad de vida relacionada con la menstruación y dolor (cuestionario breve de McGill) para evaluar los efectos del programa de ejercicios y educación en dolor. Resultados. En el grupo control, no se observaron diferencias significativas en las puntuaciones de calidad de vida relacionada con la menstruación ni en la intensidad del dolor antes y después de la intervención (p>0,05). En contraste, el grupo experimental experimentó mejoras significativas en ambas áreas después de la intervención (todos los p<0,001). Conclusiones. Este estudio demuestra que un protocolo de ejercicios y educación en dolor realizado mediante telerehabilitación tiene un impacto positivo y significativo en la calidad de vida y la intensidad del dolor percibido en mujeres jóvenes con dismenorrea primaria. Estos resultados sugieren que la telerehabilitación puede ser una estrategia efectiva para abordar este problema de salud en esta población.

Background. Primary dysmenorrhea impacts the quality of life of young women. This study investigates the effects of an exercise and pain education protocol through telerehabilitation. Objective: To determine the effects of an exercise and pain education protocol and its impact on the quality of life through telerehabilitation in young women with primary dysmenorrhea. Methods: A pre and post-test experimental study with a control group was conducted using telerehabilitation. Twenty-one young women with primary dysmenorrhea participated, randomly assigned to two groups: the experimental group (10 women) and the control group (11 women). Specific questionnaires related to menstruation-related quality of life and pain (McGill short-form questionnaire) were used to assess the effects of the exercise and pain education program. Results: In the control group, no significant differences were observed in menstruation-related quality of life scores or pain intensity before and after the intervention (p>0.05). In contrast, the experimental group experienced significant improvements in both areas after the intervention (all p<0.001). Conclusion: This study demonstrates that an exercise and pain education protocol conducted through telerehabilitation has a positive and significant impact on the perceived quality of life and pain intensity in young women with primary dysmenorrhea. These results suggest that telerehabilitation can be an effective strategy for addressing this health issue in this population.

Expectativas en salud de las personas mayores que acuden a la atención primaria / Health expectations of older people attending primary care

INTRODUCCIÓN: Desde la última década se ha evidenciado el aumento de la población de personas mayores en Chile. Muchos de ellos son usuarios regulares del sistema público de salud el cual se caracteriza por entregar una atención de tipo integral. En este sentido, resulta relevante conocer los requerimientos en salud desde la perspectiva de las experiencias de las personas mayores con respecto al uso de este servicio. OBJETIDO: El objetivo de este estudio fue identificar las expectativas de las personas mayores que asisten a los centros de APS. MATERIAL Y MÉTODOS: Este es un estudio cualitativo, descriptivo, donde la muestra fue de 13 personas mayores de 65 años y más, autovalentes, de tres centros APS, los cuales fueron entrevistados mediante instrumento semiestructurado, con análisis cualitativo de datos método que incluyó codificación abierta y focalizada. RESULTADOS: Las expectativas de las personas mayores fueron categorizadas como requerimiento de una atención profesional integral, oportunidad de atención, accesibilidad de la atención, promoción de salud sobre el autocuidado, explicación de cambios en el envejecimiento con enfoque biológico y alfabetización en salud. CONCLUSIONES: Las expectativas de las personas mayores en este estudio dan cuenta de una atención profesional integral poco efectiva, además de la necesidad de un trato especializado al grupo poblacional específico, no sólo de los profesionales, sino también del personal administrativo de los centros de APS, considerándolos una barrera en la calidad de la atención.

INTRODUCTION: Since the last decade there has been evidence of an increase in the population of older people in Chile. Many of them are regular users of the public health system (PHS) which is characterized by providing comprehensive care. In this sense, it is relevant to know the health requirements from the perspective of the experiences of the older people regarding the use of this health service. OBJECTIVE: The objective of this study was to identify the needs and expectations of older people attending PHS centers. MATERIAL AND METHODS: It were a qualitative and descriptive study. The sample was compounded by 13 people over 65 years and over, self-sufficient, from three PHS centers. It was used a semi-structured instrument. RESULTS: The main needs of the elderly were categorized as a requirement for comprehensive professional care, the opportunity for care, accessibility of care, health promotion on self-care, explanation of changes in aging with a biological focus and health literacy. CONCLUSIONS: The needs and expectations of the older people in this study account for an ineffective comprehensive professional care, in addition to the need for specialized treatment of the specific population group, not only of professionals but also of the administrative staff of the centers of PHS, considering them a barrier in the quality of care.

Somatostatin Receptor Avidity in Gastrointestinal Stromal Tumors: Theranostic Implications of Gallium-68 Scan and Eligibility for Peptide Receptor Radionuclide Therapy.

This manuscript reports on a patient with a metastatic gastrointestinal stromal tumor (GIST) refractory to standard first-line treatment, who underwent a gallium-68 scan based on pre-clinical data of somatostatin receptor (SSTR) expression in such tumors. The gallium-68 DOTATATE scan determined significant somatostatin receptor avidity as hypothesized, suggesting that this imaging modality may be used as an option for diagnostic and follow-up purposes in GIST patients. In addition, peptide receptor-mediated radiotherapy (177Lu-PPRT) via SSTR may provide a novel treatment strategy in carefully selected SSTR-avid GIST patients with thyrosine kinase inhibitor (TKI)-resistant tumors such as this case, and this warrants further investigation in novel clinical trial concepts.

Cardio-Oncology: Cancer Therapy-related Cardiovascular Complications in a Molecular Targeted Era: New Concepts and Perspectives.

Cardio-oncology is a medical discipline that identifies, prevents, and treats the cardiovascular complications related to cancer therapy. Due to the remarkable proliferation of new cancer therapies causing cardiovascular complications, such as hypertension, heart failure, vascular complications, and cardiac arrhythmia, we provide an extensive, comprehensive revision of the most up-to-date scientific information available on the cardiovascular complications associated with the use of newer, novel chemotherapeutic agents, including their reported incidence, suggested pathophysiology, clinical manifestations, potential treatment, and prevention. The authors consider this topic to be relevant for the clinicians since cardiovascular complications associated with the administration of recently approved drugs are relatively underappreciated. The purpose of this article is to provide a state-of-the-art review of cardiovascular complications associated with the use of newer, novel chemotherapeutic agents and targeted therapies, including their reported incidence, suggested pathophysiology, clinical manifestations, potential treatment, and prevention.  Ongoing efforts are needed to provide a better understanding of the frequency, mechanisms of disease, prevention, and treatment of cardiovascular complications induced by the newer, novel chemotherapeutic agents. Development of a cardio-oncology discipline is warranted in order to promote task forces aimed at the creation of oncology patient-centered guidelines for the detection, prevention, and treatment of potential cardiovascular side effects associated with newer cancer therapies.

Entrenamiento de la musculatura intrínseca del pie para la prevención de caídas en personas mayores / Effect of a program of intrinsic musculature exercises of the foot in the prevention of risk of fall on the elderly

OBJETIVO Las personas mayores y particularmente las mujeres, son propensas a sufrir traumatismo por caídas. El objetivo de esta investigación fue mejorar la estabilidad y funcionalidad de la pisada en personas mayores, implementando un programa de entrenamiento de musculatura intrínseca del pie, y determinar sus efectos en el riesgo de caída como método de prevención. MATERIALES Y METODOS Participaron 33 personas mayores, de género femenino y autovalentes. En las participantes se evaluó el equilibrio y la velocidad de la marcha con la prueba Time up and Go (TUG), y el equilibrio dinámico se evaluó con la Escala de Tinetti (ET). La intervención constó de enteramiento de tipo short-foot de forma diaria, durante 4 semanas. RESULTADOS los tiempos del TUG disminuyeron de manera progresiva al final de la intervención, lo que indica una optimización en la velocidad de la marcha, por lo que, el entrenamiento tuvo resultados beneficios para la transferencia de carga corporal de una posición sedente a bípedo y de bípedo a marcha. En cambio, para el equilibrio y marcha según ET no se detectó una diferencia significativa. CONCLUSIONES Este entrenamiento presenta una mejoría en el ámbito funcional de cambio de posición, pero no reemplaza el ajuste postural de base de sustentación para mantener el centro de masa en su posición central.

OBJETIVE Seniors, particularly women, are at risk for suffering traumatisms from falls. The objective of this study was to improve the balance and walking functionality of seniors by implementing a program to training the intrinsic muscles of the foot. The impacts of this training on preventing fall risk were assessed. MATERIALS AND METHODS A total of 33 self sufficient, female seniors participated. Balance and the speed of walking were measured using the Timed Up and Go (TUG) test, while balance and gait were measured using the Tinetti Balance and Gait Assessment Tool (TT). Intervention consisted in four weeks of daily short foot exercises. RESULTS The TUG test times decreases progressively from the start to the end of the intervention period, indicating an optimization in walking speed. This translates into beneficial results for the transfer of body load from a sedentary to standing to walking position. In contrast, balance and gait evidenced no significant changes per the TT. CONCLUSIONS The implemented training program improved the functional sphere of position change, but this did not replace the postural adjustments needed in the base of support (i.e. the feet) to maintain a well-positioned center of mass

Immune checkpoint inhibitors for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, and advanced HCC generally caries a poor prognosis. The treatment of advanced disease is limited to sorafenib, which provides only a limited improvement in survival, and novel therapies are, thus, sorely needed. Among emerging alternative approaches, immune checkpoint inhibitors are a particularly promising treatment modality. In this review, we summarize current knowledge of the mechanisms for the two primary targets of immune checkpoint inhibitors and discuss the relevance of these pathways to the immunology of HCC. We also review the state of ongoing and forthcoming trials of immune checkpoint blockade in HCC.

KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer.

This is the case of an 84-year-old woman diagnosed with Stage IVb colon adenocarcinoma (CRC) metastatic to the liver, retroperitoneum, anastomotic site, and distal rectal sigmoid colon. She experienced intolerable side effects to systemic chemotherapy with 5-fluorouracil and bevacizumab, as well as disease progression. Next generation sequencing of her tumor was ordered, and further discussion of her malignancy's genomic information took place at a multidisciplinary molecular tumor board. The patient had mutations in KRAS (Kirsten rat sarcoma viral oncogene homolog) which made her ineligible for epidermal growth factor receptor (EGFR) inhibitors; however, a KDR p.R961W c.2881C>T mutation was noted as a variant of unknown significance (VUS). KDR (kinase insert domain receptor) is the human gene encoding for vascular endothelial growth factor receptor 2 (VEGFR-2). She was then considered a suitable candidate for regorafenib, which she could only tolerate at a low dose of 40 mg daily, with the intent of prolonging her survival and to optimize her quality of life. We report her excellent tolerance and exceptional response to low dose regorafenib, including symptomatic, tumor marker, and sustained partial metabolic radiological improvement. In the largest Phase III trial of regorafenib in CRC, only five patients (1%) of 760 experienced a partial response (versus one patient, 0.4%, receiving placebo). KDR R961W mutation has been described but no functional data has been reported. This mutation occurs in the tyrosine kinase domain of the VEGFR-2. Regorafenib targets VEGFR-2 (KDR). Hereby we hypothesize KDR mutation as a novel predictive biomarker to exceptional response to regorafenib in metastatic colorectal cancer. To our knowledge, this is the first reported case of the potential correlation between KDR mutation and regorafenib use for the successful management of a patient with advanced CRC, leading to what is considered an exceptional response. Further studies based on this preliminary data are warranted.

[Herpetic encephalitis: case series of 15 patients confirmed by polymerase chain reaction]. / Encefalitis herpética: serie clínica de 15 casos confirmados por reacción de polimerasa en cadena.

Encephalitis by herpes simplex virus (HSV) is an sporadic and the most important cause of encephalitis in the western world. The aim of this study was to describe the main clinical features and response to therapy in a representative series of cases. Fifteen cases confirmed by polymerase chain reaction were identified in two university hospitals in Santiago. Average age was 41 years (range 5-78) being 80% over 30 years old. Most cases presented with fever and sensorial involvement (80%) or headache (67%) and only a minority with seizures or focal signs (< or =15%). Extracerebral herpetic lesions were present in two patients (13%). Average length of symptoms was 3. 8 days and most cases were associated to type 1 HSV (86.7%). Changes were detected in 91.7% of those evaluated with electroencephalogram, in 81.8% of those evaluated with nuclear magnetic resonance and in only 13.3% of those evaluated with a cerebral CT-scan. All patients were treated with acyclovir and case-fatality ratio was 13.3%, although one death in a patient with AIDS and CNS lymphoma could not be related to HSV. Six patients (40%) showed neurological deficit at discharge. Death or neurological deficit at discharge was associated with a delay > 3 days before acyclovir therapy. (p = 0.01, two-tailed Fisher test).

Ureteral stent insertion for gynecologic interstitial high-dose-rate brachytherapy.

PURPOSE: To determine the utility of ureteral stents in interstitial gynecological brachytherapy. METHODS AND MATERIALS: We reviewed 289 patients with cervix cancer treated with high-dose-rate interstitial brachytherapy who did not have pretreatment hydronephrosis to determine the relative incidence of benign ureteral strictures after treatment. We also did comparative dosimetry analysis in five cases of high-dose-rate brachytherapy. Bilateral ureteral stents were placed during the procedure. Three dosimetry plans were created to determine the impact of modifying clinical target volume (CTV) and applying ureteral dose constraints. In Plan 1, the ureters were contoured and excluded from the CTV and 120% dose constraints were applied. In Plan 2, the ureters were contoured and excluded, but no dose constraints were applied to the ureter. In Plan 3, the CTV was created as if the location of the ureters was unknown and then ureteral dose was determined. RESULTS: There were 11 ureteral strictures observed in 255 nonstented cases and 0 ureteral strictures in 34 stented cases. Plan 1 reduced the ureter dose (D(0.1cc)) by a median 22% (7.0-53.8%) compared with Plan 2 and by a median of 30.9% (12.3-65%). compared with Plan 3. CONCLUSIONS: Placement of stents and ureteral dose constraints facilitates dosimetry and reduces the dose to ureters. Temporary ureteral stents prevent obstruction during interstitial gynecologic brachytherapy and allows the ureters to be addressed as an organ at risk.