Lifestyle interventions in the management of systemic sclerosis: a systematic review of the literature.

Objectives: We aimed to investigate the efficacy of lifestyle interventions for the management of SSc. Methods: We searched the MEDLINE, Embase, Web of Science and CINAHL databases in June 2021. We included studies conducted on five or more patients with SSc published between 1 January 2000 and the search date evaluating lifestyle interventions, excluding systematic reviews without meta-analyses. Critical appraisal was conducted using critical appraisal tools from the Joanna Briggs Institute. Thirty-six studies were included for full-text evaluation. Results: A total of 17 studies evaluated the effect of physical exercise alone, whereas 14 studies evaluated educational interventions for mental health management, often with physical exercise as a central component. At an aggregated level, these studies support patient education and physical exercise for the improvement of physical function, in particular hand and mouth function. Studies on diet and nutrition were few (n = 5) and pertained to gastrointestinal as well as anthropometric outcomes; these studies were insufficient to support any conclusions. Conclusion: Physical exercise and patient education should be considered for improving physical function in patients with SSc. These interventions can be provided alongside pharmacotherapy, but there is no evidence supporting that they can be a substitute. Further research should aim at assessing the effects of reductions of harmful exposures, including tobacco smoking and alcohol, improving sleep and enhancing social relations, three hitherto underexplored facets of lifestyle in the context of SSc.

Test-Retest Reliability of Isokinetic Strength in Lower Limbs under Single and Dual Task Conditions in Women with Fibromyalgia.

Background: Previous research has established good test-retest reliability for isokinetic dynamometry in fibromyalgia. However, the reliability of this test under dual-task conditions has not been investigated in fibromyalgia. Methods: A total of 10 women with fibromyalgia participated in this study. Participants completed the concentric/concentric test. The dual-task condition involved subtracting two by two while performing the test. Results: Reliability analysis under the single condition showed "poor" to "excellent" values for maximum peak torque in knee extension and "moderate" to "excellent" values for average. "Poor" to "excellent" reliability values were found in knee flexion for the maximum and average. Dual-task condition in knee extension ranged from "moderate" to "excellent" for maximum and average values, and in knee flexion, it ranged from "poor" to "excellent" for maximum value and from "moderate" to "excellent" for average value. Conclusions: Isokinetic dynamometry demonstrated sufficient reliability for measuring strength in knee extension maximum and average during single-task and dual-task conditions, along with knee flexion dual-task average in fibromyalgia. For knee flexion single-task maximum and average and knee flexion dual-task maximum, we did not obtain sufficiently reliable measurements. Only the concentric/concentric test has been studied, and future studies with a larger sample size are needed in order to generalize the results.

Radioterapia preoperatoria en cáncer de mama como estrategia terapéutica, a propósito de un caso / Preoperative radiotherapy in breast cancer as a therapeutic strategy, case report

Múltiples estrategias terapéuticas se han desarrollado con el objetivo de optimizar el tratamiento del cáncer de mama, especialmente antes de ir a quirófano, desde la introducción de la quimioterapia preoperatoria por Fisher. Una de estas ha sido la radioterapia, la cual tiene beneficios claros en esa patología, pues reduce a la mitad el riesgo de recurrencia, y disminuye la muerte por cáncer de mama en aproximadamente una sexta parte después de cirugía conservadora. Aunque no se suele considerar antes de la cirugía, el uso de radioterapia preoperatoria en cáncer de mama, no es nuevo, y se ha demostrado que esta alternativa terapéutica es factible, bien tolerada y asociada a una tasa de respuesta patológica completa del 10 % -40 %. Se presenta el caso de una paciente con cáncer de mama metastásico, quien recibió múltiples esquemas de quimioterapia y a quien se le planteó radioterapia preoperatoria, recibiendo la misma con muy buena respuesta, sin aumentar la dificultad técnica para la realización de la intervención quirúrgica, y sin complicaciones asociadas a la herida operatoria. En la actualidad, existen pocos estudios clínicos sobre radioterapia preoperatoria, y su efecto en las pacientes con cáncer de mama localmente avanzado, es controvertido. Al observar en la biopsia definitiva respuesta patológica completa, es un indicio de cómo la radioterapia preoperatoria en cáncer de mama podría ser una opción en casos complejos con poca respuesta a la terapia convencional(AU)

Multiple therapeutic strategies have been developed with the aim of optimizing breast cancer (BC) treatment, especially preoperatively since the introduction of preoperative chemotherapy by Fisher. One of these has been radiation therapy (RT), which has clear benefits in breast cancer, halving the risk of recurrence andreducing breast cancer death byapproxmatelyone-sixth after breast-conserving surgery. Although not often considered for use prior to surgery, the use of preoperativeradiotherapy in localized breast cancer is not new andhas demonstrated that this therapeutic alternative is feasible, well tolerated and associated with a pathologic complete response rate of 10-40%. We present the case of a patient with metastatic breast cancer who received multiple chemotherapy schedules and who was considered preoperative radiotherapy, receiving the same with very good response, without increasing the technical difficulty for the performance of surgery, and without complications associated with the operative wound. At present, there are few clinical studies on preoperative radiotherapy, and its effect in patients with locally advanced breast cancer is controversial. And although this is a single case, observing a complete pathologic response in the definitive biopsy gives us a great indication of how preoperative radiotherapy in breast cancer could be an option in complex cases with little response to conventional therapy(AU)

Efficacy of lifestyle interventions in the management of systemic lupus erythematosus: a systematic review of the literature.

We performed a systematic review to explore existing evidence regarding the efficacy of lifestyle interventions for the management of systemic lupus erythematosus (SLE). The search was conducted on the 22nd of June 2021 for publications between 1st of January 2000 and the date of search. Additional articles within the aforementioned timeframe and until December 2023 were added by hand searching. Databases utilized were Medline, Embase, Web of Science, and Cinahl. Lifestyle interventions were defined as any intervention encompassing one or more of the following: physical exercise, diet and nutrition, mental health, harmful exposures, sleep, and social relations. The Joanna Briggs Institute critical appraisal tools were used for risk of bias assessment. The search yielded 11,274 unique records, we assessed the full text of 199 records, and finally included 102 studies. Overall, the quality of the evidence is limited, and there were multiple sources of heterogeneity. The two domains most extensively researched were mental health (40 records) and physical exercise (39 records). Psychological interventions had a positive effect on depressive symptoms, anxiety, and health-related quality of life (HRQoL), whereas physical exercise improved fatigue, depressive symptoms, aerobic capacity, and physical functioning. Studies on diet and nutrition (15 records) support that low fat intake and Mediterranean diet may be beneficial for reducing cardiovascular risk, but large interventional studies are lacking. Studies on harmful exposures (7 records) support photoprotection and use of sunscreen. While studies imply benefits regarding disease burden and drug efficacy in non-smokers and regarding HRQoL in normal-weight patients, more survey is needed on tobacco smoking and alcohol consumption, as well as weight control strategies. Studies on social relations (1 record) and sleep (no records) were sparse or non-existent. In conclusion, psychosocial interventions are viable for managing depressive symptoms, and exercise appears essential for reducing fatigue and improving aerobic capacity and physical function. Photoprotection should be recommended to all patients. Lifestyle interventions should be considered a complement, not a substitute, to pharmacotherapy.

Obesity and tobacco smoking are independently associated with poor patient-reported outcomes in SLE: a cross-sectional study.

We investigated associations of obesity and tobacco smoking with health-related quality of life (HRQoL), pain, fatigue, and functional impairment in systemic lupus erythematosus (SLE). Furthermore, we explored whether there was an effect modification between these two factors. We included adult SLE patients from the Linköping University Hospital (n = 325) in the present cross-sectional analysis. We further included population-based controls and performed cardinality matching to balance age and sex distributions with cases (n = 224). HRQoL was assessed with the EQ-5D index score; pain, fatigue, and overall SLE-related health state with visual analogue scales (VAS; 0 [best] to 100 [worst]); and functional impairment with the HAQ-DI. Unacceptable outcomes were defined as VAS scores corresponding to the 90th percentile derived from the matched controls. SLE patients reported worse scores than controls in all measures, and approximately 30% experienced unacceptable outcomes. When compared with normal-weight, obese SLE patients reported lower HRQoL, and greater functional impairment and risk of unacceptable pain (OR: 3.2; 95% CI 1.6-6.7) and fatigue (OR: 2.1; 95% CI 1.0-4.3). Similarly, the current smokers reported higher levels of functional impairment and a greater risk of unacceptable pain (OR: 3.8; 95% CI 1.8-8.2) and fatigue (OR: 2.8; 95% CI 1.3-5.9) than never smokers. The associations were independent of age, sex, disease duration, disease activity, and organ damage. There was no evidence of a synergistic effect between increased BMI and smoking on any outcome. In summary, obesity and smoking are risk factors for unacceptable patient-reported outcomes in SLE, regardless of clinical activity.

Mortalidad Materna en Venezuela: aspectos médicos y Políticas (1940 - 2016) / Materna Mortality in Venezuela: medical issues and Public Policy (1940 - 2016)

En la actualidad Venezuela se encuentra en una crisis social y económica sin precedentes. La mortalidad materna(MM) es un indicador en salud importante, debido a que permite tener idea de la atención médica de un país; se mide a través de dos indicadores: Razón de Mortalidad Materna (RMM) y Tasa de Mortalidad Materna (TMM). Objetivo: Revisar y compararla evolución de ambos indicadores de MM desde la década de 1930 hasta la década 2000. Métodos: Se realizó una revisión de la literatura y de informes técnicos de organismos gubernamentales y no gubernamentales para el análisis de la situación previa y reciente de esta situación en Venezuela. Los resultados señalan que existe una notable disminución de las cifras de MM como ha de esperarse con el mejoramiento de la tecnología desde la década de 1930 hasta el año 2000; posteriormente ocurre un retroceso de la sanidad pública con cifras comparables a la década de 1960. Concluimos que la MM ha sido desde tiempos pasados un problema constante en la salud pública; al pasar los años y gobiernos, se han implementado numerosas políticas públicas para mejorar esta situación, muchas de estas estrategias han sido fallidas debido a la falta de su continuidad y de su cumplimiento pleno.

Venezuela is currently in an unprecedented socialand economic crisis. Maternal mortality is an important health indicator because it provides an idea of a country's medical care. Maternal mortality is usually measured through two indicators: Maternal Mortality Ratio (MMR) and Maternal Mortality Rate. Objective: Review and compare the evolution of both healthindicators from the 1930s to 2016. Methods: A review of the literature and technical reports from governmental andnon-governmental organizations was carried out to analyze theprevious and recent situation. of this situation in Venezuela. Theresults indicate that there is a notable decrease in the figures ofmaternal mortality, as should be expected with the improvementof technology from the 1930s to the year 2000. Subsequently, there is a decline in public health with figures comparable to the1960s. We conclude that maternal mortality has been a constant problem in public health since ancient times. Over the years and governments, numerous public policies have been implementedto improve this situation. Many of these strategies have beenfailed due to lack of continuity and in the absence of its full compliance.

Non-functional Pituitary Adenomas: Analysis of Delayed Diagnosis in Mexico.

BACKGROUND:  Although tumors of the central nervous system (CNS) are rare, they can cause significant morbidity and mortality. The clinical presentation of patients with non-functional pituitary adenomas (NFPA) ranges from being completely asymptomatic to causing pituitary, hypothalamic, or visual dysfunction due to their large size. Patients usually arrive with large tumors at the time of diagnosis.  Objectives: Try to describe the characteristics of NFPA and explain the causes of delayed diagnosis.  Methods: We carried out a retrospective study including 58 patients with NFPA and analyzed the tumor volume at the time of diagnosis and its relationship with sociodemographic and health sector variables.  Results: Low socioeconomic status (SES) was associated with high tumor volume (SES 1-2 of 17.4 cm3 vs 3-6 of 11.7 cm3, p=0.018), and the time between first consultation and diagnosis was longer in the public sector than in the private sector (13.5 months vs 5.1 months). The time between the first symptom and the first consultation was shorter when they had visual impairment than when they did not (4.1 vs 18.4 months, p=0.006). CONCLUSIONS: On the one hand, citizens should be made aware that a visual deficit should make them go to a medical check-up, and on the other hand, strengthen the health system so that they have the NFPA as a differential diagnosis in patients with some visual alteration. Socioeconomic inequality in our country undoubtedly puts the underprivileged at greater risk.

Randomised placebo-controlled clinical trial evaluating the impact of a new visual rehabilitation program on neuroadaptation in patients implanted with trifocal intraocular lenses.

PURPOSE: To evaluate the efficacy of a new visual training program for improving the visual function in patients implanted with trifocal intraocular lenses (IOLs). METHODS: Randomised placebo-controlled clinical trial enrolling 60 subjects (age, 47-75 years) undergoing cataract surgery with implantation of trifocal diffractive IOL. Home-based active visual training was prescribed immediately after surgery to all of them (20 sessions, 30 min): 31 subjects using a serious game based on Gabor patches (study group) and 29 using a placebo software (placebo group). Visual acuity, contrast sensitivity (CS), and perception of visual disturbances (QoV questionnaire) were evaluated before and after training. Likewise, in a small subgroup, resting-state functional magnetic resonance imaging (rs-fMRI) analysis was performed. RESULTS: No significant differences were found between groups in compliance time (p = 0.70). After training, only significant improvements in monocular uncorrected intermediate visual acuity were found in the study group (p ≤ 0.01), although differences between groups did not reach statistical significance (p ≥ 0.11). Likewise, significantly better binocular far CS values were found in the study group for the spatial frequencies of 6 (p = 0.01) and 12 cpd (p = 0.03). More visual symptoms of the QoV questionnaire experienced a significant change in the level of bothersomeness in the study group. Rs-fMRI revealed the presence significant changes reflecting higher functional connectivity after the training with the serious game. CONCLUSIONS: A 3-week visual training program based on the use of Gabor patches after bilateral implantation of trifocal diffractive IOLs may be beneficial for optimising the visual function, with neural changes associated suggesting an acceleration of neuroadaptation. Trial registration ClinicalTrials.gov, NCT04985097. Registered 02 August 2021, https://clinicaltrials.gov/(NCT04985097 ).

[Deep brain stimulation for Parkinson's disease: experience, benefits and limitations in a center in Latin America]. / Estimulación cerebral profunda para enfermedad de Parkinson: experiencia, beneficios y limitaciones en un centro en Latinoamérica.

Background: Parkinson's disease is poorly studied in Colombia. It is pharmacologically managed, but for refractory cases, surgery is a therapeutic option, positively impacting on quality of life. Objective: To determine the impact of deep brain stimulation as management in the control of progression in patients with Parkinson's disease attended our institution between the years 2014 to 2020. Method: Descriptive retrospective study, with patients collected between 2014 and 2020 undergoing deep brain stimulation surgery. The MDS-UPDRS (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale) was applied in the pre- and postoperative period, and the results were compared. Results: 21 patients were included and the UPDRS was applied, finding a decrease in scores in the postoperative period. One patient had an operative site infection. Conclusions: There was an improvement in the MDS-UPDRS score, with a low rate of complications. The procedure time was prolonged from the preoperative evaluation. Deep brain stimulation is the management of choice for refractory Parkinson's disease. The patients in this series showed improvement in their symptoms. Unfortunately, there are limitations to perform this procedure in Colombia, such as the delay in the authorization of the procedure.

Antecedentes: La enfermedad de Parkinson está poco estudiada en Colombia. Es de manejo farmacológico, pero para casos refractarios la cirugía es una opción terapéutica que impacta positivamente en la calidad de vida. Objetivo: Determinar el impacto de la estimulación cerebral profunda como manejo en el control de la progresión en pacientes con enfermedad de Parkinson atendidos nuestra institución entre los años 2014 a 2020. Método: Estudio descriptivo de corte retrospectivo con pacientes recolectados entre los años 2014 y 2020 sometidos a cirugía de estimulación cerebral profunda. Se aplicó la MDS-UPDRS (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale) en el pre- y el posoperatorio, y se compararon los resultados. Resultados: Se incluyeron 21 pacientes y se les aplicó la MDS-UPDRS, encontrando una disminución en las puntuaciones en el posoperatorio. Un paciente presentó infección del sitio operatorio. Conclusiones: Hubo mejoría en la puntuación de la MDS-UPDRS, con baja tasa de complicaciones. El tiempo de realización del procedimiento fue prolongado desde la valoración preoperatoria. La estimulación cerebral profunda es el manejo de elección para la enfermedad de Parkinson refractaria. Los pacientes de esta serie mostraron mejoría en sus síntomas. Desafortunadamente, existen limitaciones para la realización de este procedimiento en Colombia, como el retraso en la autorización del procedimiento.

Angiosarcoma gastrointestinal multifocal, con compromiso extenso de estómago, intestino delgado y colon. Reporte de un caso / Multifocal gastrointestinal angiosarcoma, with extensive gastric, small intestine and colon involvement. A case report

Introducción. El angiosarcoma es una neoplasia vascular originada a nivel del endotelio, de baja frecuencia, conocido por su agresividad y crecimiento acelerado. Alcanza solo el 1 al 2 % del total de los sarcomas. La presentación gastrointestinal es infrecuente y su incidencia es poco conocida debido al escaso reporte de casos en la literatura. Suele identificarse en etapas avanzadas debido a la dificultad del diagnóstico histopatológico por sus características morfológicas, siendo necesario aplicar tinciones especiales o estudio inmunohistoquímico. Caso clínico. Por su interés y singularidad, presentamos el caso de un paciente masculino de 54 años, quien consultó con hemorragia digestiva profusa, anemización y requerimiento de terapia transfusional. Resultados. Durante el proceso diagnóstico, en la endoscopia encontraron diversas lesiones multifocales que se extendían por gran parte del tracto gastrointestinal. El estudio histopatológico mostró angiosarcoma gastrointestinal. Discusión. El angiosarcoma del tracto gastrointestinal es extremadamente infrecuente, de difícil diagnóstico y bajas posibilidades de manejo curativo, con opciones terapéuticas limitadas, lo que configura un mal pronóstico a corto plazo

Introduction. Angiosarcoma is a vascular neoplasm originating from endothelial cells, known for its aggressiveness, accelerated growth and reduced frequency. Reach only 1 to 2% of total sarcomas. Gastrointestinal presentation is extremely rare, the true incidence is poorly known, due to the limited reports of this entity in the literature. It is usually identified in advanced stages in view of the difficulty of the histopathological diagnosis, attributable to its morphological characteristics, being necessary to apply special stains or immunohistochemical study. Case report. Due to their interest and uniqueness, we present the case of a 54-year-old male patient, who presented with a profuse gastrointestinal bleeding, anemia, and requirement for transfusion therapy. Results. The endoscopy detected several multifocal lesions that extended most of the gastrointestinal tract. The histopathological study showed gastrointestinal angiosarcoma. Discussion. Angiosarcoma of the gastrointestinal tract is extremely uncommon, difficult to diagnose and has low possibilities of curative management, with limited therapeutic options, which configures a poor prognosis in the short term

Is there the same requirement to obtain the PhD degree in all the departments of surgery of the Spanish universities?

INTRODUCTION: The doctorate is the third cycle of official university studies, which, through the defense of the doctoral thesis leads to the acquisition of the title of doctor or PhD from the Anglo-Saxon countries. Royal Decree law 99/2011 regulates doctoral programs, with a wide margin on quality requirements. The objective of this study is to find out if there is this variation in the requirements of the doctorate programs of the different departments of surgery of the Spanish public universities and to establish a quality scale. METHODS: Cross-sectional observational study from 2/22/2021 to 3/3/2021, through a survey sent electronically to the professors of the departments of surgery. RESULTS: Thirty-five departments of surgery were consulted, obtaining a response in 29 of them (82.9%). The observed variation regarding requirements has been basically in the quality of the research project, in fact in 25 (86.2%) there are no regulations on this. When it is presented in the form of a compendium of articles, these are required to be original in 15 (51.7%). Regarding the position as author, the doctoral student must be the preferred author, at least in 2 articles in 14 (48.4%) of the programs. In 14 departments (48.4%) there are no regulations on the position of the articles and quartiles of journals. When scoring the different programs according to their requirements, the variability is high, ranging between 2 and 19 points. Funding for the development of the doctorate is meager. CONCLUSIONS: There is a wide variability in the requirement of doctoral programs. Homogeneous levels of demand must be defined to promote and protect higher-level doctorates.

Subthalamic Beta Activity in Parkinson's Disease May Be Linked to Dorsal Striatum Gray Matter Volume and Prefrontal Cortical Thickness: A Pilot Study.

Background: Excessive oscillations at beta frequencies (13-35 Hz) in the subthalamic nucleus (STN) represent a pathophysiological hallmark of Parkinson's disease (PD), which correlates well with parkinsonian symptoms and is reduced in response to standard disease treatments. However, the association of disease-specific regional gray matter (GM) atrophy or cortical thickness (CT) with the presence of STN beta oscillatory activity has been poorly investigated but is of relevance given the potential of these variables for extracting information about PD pathophysiology. This exploratory study investigated the involvement of regional GM volume and CT in the basal ganglia-cortical network and its potential association with the presence of STN beta oscillatory activity in PD. Methods: We acquired preoperative GM densities on T1-weighted magnetic resonance imaging scans and we carried out regional estimation of GM volume and CT. LFP activities from the STN were recorded post-operatively in 7 cognitively preserved PD patients off dopaminergic medication undergoing deep-brain stimulation surgery. Oscillatory beta power was determined by power spectral density of 4-min resting state STN LFP activity. Spearman partial correlations and regression analysis were used to screen the presence of STN beta power for their relationship with GM volume and CT measurements. Results: After controlling for the effects of age, educational level, and disease duration, and after correcting for multiple testing, enhanced STN beta power showed significant and negative correlations between, first, volume of the right putamen and left caudate nucleus, and second, smaller CT in frontal regions involving the left rostral middle frontal gyrus (MFG) and left medial orbitofrontal gyrus. A lower volume in the right putamen and a lower CT in the left MFG demonstrated the strongest associations with increased STN beta power. Conclusions: These tentative results seem to suggest that STN LFP beta frequencies may be mainly linked to different but ongoing parallel neurodegenerative processes, on the one hand, to GM volume reduction in dorsal striatum, and on the other hand, to CT reduction of prefrontal-"associative" regions. These findings could further delineate the brain structural interactions underpinning the exaggerated STN beta activity commonly observed in PD patients.

Effects of Transcranial Direct Current Stimulation on Brain Electrical Activity, Heart Rate Variability, and Dual-Task Performance in Healthy and Fibromyalgia Women: A Study Protocol.

People with fibromyalgia could experience physical and cognitive impairments. Furthermore, when performing two tasks at the same time, people with fibromyalgia showed a higher dual-task cost compared to a single task than healthy people. This may result in poorer performance of activities of daily living that are commonly presented as a combination of two or more tasks. Transcranial direct current stimulation (tDCS) is a promising nonpharmacological therapy. However, there is controversy regarding the intensities and the effectiveness of this therapy. Thus, the present study will aim: (1) to compare the effectiveness and the impact of two tDCS intensities (1 mA and 2 mA) on cognitive, motor, brain functions, and cardiac autonomic modulation; (2) to study the impact of tDCS on the dual-task performance and creativity after applying tDCS in dorsolateral prefrontal cortex. In this study, 26 women will participate and will be divided into two groups: women with fibromyalgia (n = 13), and healthy controls (n = 13). A reduction in cognitive-motor interference in dual-task performance is expected, as well as a modification in neurophysiological parameters and an improvement in cardiac autonomic modulation. Lastly, no different effects are expected depending on the stimulation intensity applied. The obtained results will help to determine if tDCS in the dorsolateral prefrontal cortex could improve the occupational performance of women with fibromyalgia.

Structural, biochemical, and functional properties of the Rap1-Interacting Adaptor Molecule (RIAM).

Leukocytes, the leading players of immune system, are involved in innate and adaptive immune responses. Leukocyte adhesion to endothelial cells during transmigration or to antigen presenting cells during T cell activation, requires integrin activation through a process termed inside-out integrin signaling. In hematopoietic cells, Rap1 and its downstream effector RIAM (Rap1-interacting adaptor molecule) form a cornerstone for inside-out integrin activation. The Rap1/RIAM pathway is involved in signal integration for activation, actin remodeling and cytoskeletal reorganization in T cells, as well as in myeloid cell differentiation and function. RIAM is instrumental for phagocytosis, a process requiring particle recognition, cytoskeletal remodeling and membrane protrusion for engulfment and digestion. In the present review, we discuss the structural and molecular properties of RIAM and the recent discoveries regarding the functional role of the Rap1/RIAM module in hematopoietic cells.

Real-world evaluation of molecular testing and treatment patterns for EGFR mutations in non-small cell lung cancer in Latin America.

Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lung cancer (NSCLC) being the most prevalent. The current study aimed to report real-world data on epidermal growth factor receptor (EGFR) mutational testing and treatment regimens at diagnosis and progression in patients with metastatic NSCLC across four Latin American countries (Argentina, Chile, Colombia and Uruguay). A retrospective, multicenter, observational study was conducted in patients with NSCLC using medical records from participating countries. The study population was categorized into two cohorts: Cohort 1 comprised of newly diagnosed, treatment-naïve patients with stage IV NSCLC; and cohort 2 comprised of stage IV NSCLC EGFR mutation (EGFRm)-positive patients who had progressed after first- or second-generation EGFR-tyrosine kinase inhibitor (TKI) treatment. Measures included demographic variables, health characteristics, treatment regimen, molecular testing rate and turnaround time at diagnosis and at progression for cohorts 1 and 2, respectively. Descriptive statistics were used to summarize all study measures. Of the 462 patients enrolled, 431 were newly diagnosed or treatment naïve with metastatic NSCLC. In cohort 1, the majority of patients with private health insurance (57.31%) underwent molecular diagnosis while only 41.3% of patients within the public sector had access to testing. The average molecular testing rate in cohort 1 varied across countries, with Argentina having the highest testing rate (79%) and Uruguay the lowest (27.63%). EGFRm was observed in 22% of patients. Cohort 2 comprised 31 patients who had progressed after first- or second-generation EGFR-TKI treatment and of these, only 22 (70.97%) underwent testing after progression. Access to molecular testing is still a challenge impacting the choice of first-line treatment in Latin American patients with NSCLC. These findings underline the unmet needs of ensuring early diagnosis, molecular profiling and use of correct treatment to alleviate NSCLC burden in the region.

Prevalencia y manejo de anemia en enfermedad inflamatoria intestinal en un centro de referencia en Colombia / Prevalence and treatment of anemia in inflammatory bowel disease in a Colombian reference center

Resumen Introducción: la anemia es la complicación más frecuente en enfermedad inflamatoria intestinal (EII). El objetivo de este estudio fue determinar la prevalencia, asociaciones y tratamiento de la anemia en EII en nuestro medio. Materiales y métodos: se analizaron de forma retrospectiva datos de pacientes adultos con EII del Hospital Pablo Tobón Uribe en Medellín, Colombia, que consultaron desde 2001 hasta febrero de 2019. Se emplearon frecuencias absolutas y relativas. Para comparar dos proporciones se utilizó la prueba de chi cuadrado de independencia y se estimó el Odds ratio (OR). Resultados: se documentaron 759 pacientes con EII, de los cuales 544 (71,6 %) presentaron colitis ulcerativa (CU); 200 (26,3 %), enfermedad de Crohn (EC), y 15, EII no clasificable (1,9 %). En total, 185 (24,4 %) pacientes con EII presentaron anemia, que es menos frecuente en CU que en EC (22,2 % frente a 32,5 %, respectivamente; OR: 0,684; IC: 0,456-0,96; p = 0,03). Los pacientes con CU extensa (54,1 %) tenían más anemia que aquellos con CU no extensa (46,3 %) (OR: 4,4; IC: 2,6-7,4; p = 0,001); lo mismo se observó al comparar la CU grave (66,1 %) con la no grave (32,3 %) (OR: 4,95; IC: 2,87-8,51; p = 0,000). En la EC, los pacientes con comportamiento no inflamatorio (B2, B3: 73,9 %) presentaron más anemia en comparación con aquellos con comportamiento inflamatorio (B1: 26,2 %) (OR: 0,35; IC: 0,18-0,67; p = 0,000). 44,3 % de los pacientes no recibió tratamiento, 19,5 % recibió hierro oral, 20,0 % recibió hierro intravenoso y 16,2 % fue transfundido. Conclusiones: la anemia es una complicación frecuente de la EII en nuestro medio (24,4 %). A pesar de las guías internacionales, el tratamiento es subóptimo en nuestro medio.

Abstract Introduction: Anemia is the most frequent complication of inflammatory bowel disease (IBD). This study aims to determine the prevalence, connection, and treatment of anemia in IBD in a local context. Materials and Methods: This retrospective study was conducted at The Pablo Tobon Uribe Hospital, in Medellín (Colombia) with adult patients who (were admitted) came for consultation from 2001, until February 2019. Absolut and relative frequencies were calculated. The Chi square test of independence was applied for comparing two proportions and the odds ratio (OR) was estimated. Results: A total of 759 IBD patients were enrolled, 544 (71.6%) with ulcerative colitis (UC); 200 (26.3%) Crohn's disease (CD), and 15 (1.9%) with non-classifiable IBD. In total, 185 (24,4 %) IBD patients had a diagnosis of anemia, that is less frequent in UC patients that in CD patients (22,2 % versus 32,5 %, respectively; OR: 0,684; CI: 0,456-0,96; p = 0,03). Extensive UC patients (54,1 %) had a more recurrent level of anemia than non-extensive UC (46,3 %) (OR: 4,4; CI: 2,6-7,4; p = 0,001); the same result was observed when severe UC (66,1 %) was compared with UC non-severe (32,3 %) (OR: 4,95; CI: 2,87-8,51; p = 0,000). In the analysis of CD, patients with a non-inflammatory response (B2, B3: 73,9 %) had a more recurrent level of anemia than patients with an inflammatory response (B1: 26,2 %) (OR: 0,35; CI: 0,18-0,67; p = 0,000). 44,3 % of the total number of patients received treatment, 19,5 % received oral iron, 20,0 % received intravenous iron, and 16,2 % received a blood transfusion. Conclusions: In our context, Anemia is a common complication in IBD cases (24,4 %). Despite the existence of international guidelines, the treatment in our context is not optimal.

Cellular Integrin α5ß1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells.

Approximately 25% of colorectal cancer (CRC) patients develop peritoneal metastasis, a condition associated with a bleak prognosis. The CRC peritoneal dissemination cascade involves the shedding of cancer cells from the primary tumor, their transport through the peritoneal cavity, their adhesion to the peritoneal mesothelial cells (PMCs) that line all peritoneal organs, and invasion of cancer cells through this mesothelial cell barrier and underlying stroma to establish new metastatic foci. Exosomes produced by cancer cells have been shown to influence many processes related to cancer progression and metastasis. In epithelial ovarian cancer these extracellular vesicles (EVs) have been shown to favor different steps of the peritoneal dissemination cascade by changing the functional phenotype of cancer cells and PMCs. Little is currently known, however, about the roles played by exosomes in the pathogenesis and peritoneal metastasis cascade of CRC and especially about the molecules that mediate their interaction and uptake by target PMCs and tumor cells. We isolated exosomes by size-exclusion chromatography from CRC cells and performed cell-adhesion assays to immobilized exosomes in the presence of blocking antibodies against surface proteins and measured the uptake of fluorescently-labelled exosomes. We report here that the interaction between integrin α5ß1 on CRC cells (and PMCs) and its ligand ADAM17 on exosomes mediated the binding and uptake of CRC-derived exosomes. Furthermore, this process was negatively regulated by the expression of tetraspanin CD9 on exosomes.

Is there the same requirement to obtain the PhD degree in all the departments of surgery of the Spanish universities? / ¿Existe la misma exigencia en la obtención del doctorado (PhD) en todos los departamentos de cirugía de las universidades españolas?

INTRODUCTION: The doctorate is the third cycle of official university studies, which, through the defense of the doctoral thesis leads to the acquisition of the title of doctor or PhD from the Anglo-Saxon countries. Royal Decree law 99/2011 regulates doctoral programs, with a wide margin on quality requirements. The objective of this study is to find out if there is this variation in the requirements of the doctorate programs of the different departments of surgery of the Spanish public universities and to establish a quality scale. METHODS: Cross-sectional observational study from 2/22/2021 to 3/3/2021, through a survey sent electronically to the professors of the departments of surgery. RESULTS: Thirty-five departments of surgery were consulted, obtaining a response in 29 of them (82.9%). The observed variation regarding requirements has been basically in the quality of the research project, in fact in 25 (86.2%) there are no regulations on this. When it is presented in the form of a compendium of articles, these are required to be original in 15 (51.7%). Regarding the position as author, the doctoral student must be the preferred author, at least in 2 articles in 14 (48.4%) of the programs. In 14 departments (48.4%) there are no regulations on the position of the articles and quartiles of journals. When scoring the different programs according to their requirements, the variability is high, ranging between 2 and 19 points. Funding for the development of the doctorate is meager. CONCLUSIONS: There is a wide variability in the requirement of doctoral programs. Homogeneous levels of demand must be defined to promote and protect higher-level doctorates.

Functional Integrin Regulation Through Interactions with Tetraspanin CD9.

Integrins are adhesion receptors that mediate many intercellular and cell-extracellular matrix interactions with relevance in physiology and pathology. Unlike other cellular receptors, integrins critically require activation for ligand binding. Through interaction in cis with other molecules and the formation of tetraspanin-enriched membrane microdomains (TEMs), the tetraspanin CD9 regulates integrin activity and avidity. Here we present three techniques used to study CD9-integrin interactions and integrin activation.

Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis.

OBJECTIVES: In patients with LN, clinical and histological responses to treatment have been shown to be discordant. We investigated whether per-protocol repeat kidney biopsies are predictive of LN relapses and long-term renal function impairment. METHODS: Forty-two patients with incident biopsy-proven active proliferative (class III/IV±V) LN from the database of the UCLouvain were included in this retrospective study. Per-protocol repeat biopsies were performed after a median [interquartile range (IQR)] time of 24.3 (21.3-26.2) months. The National Institutes of Health activity index (AI) and chronicity index (CI) scores were assessed in all biopsies. RESULTS: Despite a moderate correlation between urinary protein/creatinine ratios (UPCR) and AI scores at repeat biopsy (r = 0.48; P = 0.001), 10 patients (23.8%) with UPCR < 1.0 g/g still had a high degree of histological activity (AI > 3). High AI scores (continuous) in repeat biopsies were associated with an increased probability and/or shorter time to renal relapse (n = 11) following the repeat biopsy [hazard ratio (HR) = 1.2, 95% CI: 1.1, 1.3; P = 0.007], independently of proteinuria levels. High CI scores (continuous) in repeat biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR = 1.8, 95% CI: 1.1, 2.9; P = 0.016) through a median (IQR) follow-up time of 131.5 (73.8-178.2) months, being also the case for acute tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in repeat but not baseline biopsies. CONCLUSION: Our results highlight the usefulness of per-protocol repeat biopsies, herein performed after a median time of 24 months from baseline, as an integral part of the treatment evaluation, also in patients showing adequate clinical response.