Who are we missing? Language exclusivity of patient-reported outcomes in atrial fibrillation clinical trials.

INTRODUCTION: Patient-reported outcomes (PROs) are increasingly used to evaluate quality of life (QoL) in Atrial Fibrillation (AF) patients, providing crucial insights in clinical trials. This study examines the frequency of PRO use in AF trials and the linguistic accessibility of AF-specific PROs. BACKGROUND: As the United States becomes more multilingual, ensuring PROs are available in various languages is vital. The number of people speaking a language other than English at home has tripled from 23.1 million in 1980 to 67.8 million in 2019. This diversity necessitates the availability of PROs in multiple languages for inclusive clinical assessments. METHODS: We queried ClinicalTrials.gov for all US interventional AF trials up to November 28, 2023, reviewing each for PRO usage as primary or secondary outcomes. We identified the five most common AF-specific and generic PROs, extracting their available translations and original languages from published sources. RESULTS: Of 233 identified trials, 191 had associated publications, with 180 (94.2%) conducted solely in English. Only one trial (0.4%) used an AF-specific PRO as a primary outcome, compared to four (1.7%) with a generic PRO. Ten trials (4.3%) used AF-specific PROs as secondary endpoints, versus 22 (9.4%) using generic PROs. AF-specific PROs had significantly fewer translations than generic PROs (11.2 vs. 148.8; p < .001). The AF Effect on Quality-of-Life (AFEQT) was available in 24 languages, with limited translations in commonly spoken US languages like Arabic and Asian languages. CONCLUSION: The limited availability of AF-specific PRO translations highlights a barrier to inclusive AF clinical trials. Expanding translations for AF-specific PROs is crucial for equitable QoL assessments.

Preoperative brachytherapy for early-stage cervical cancer: Systematic review and meta-analysis.

OBJECTIVE: To assess the rate of pathological response rate, and the oncological outcomes of preoperative brachytherapy (PBT) in early-stage cervical cancer. METHODS: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA) statement. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2022. Only English and French articles were included. Studies containing data about pathology response or oncological outcomes among patients who received PBT as compared to those who underwent up-front surgery in early-stage cervical cancer were included. This study was registered in PROSPERO (CRD42022319036). RESULTS: Thirteen studies met the inclusion criteria, 3 randomized controlled trials (RCT), and 10 non-randomized studies (NRS). The 5-year survival was significantly higher in the PBT group compared with the up-front surgery group (OR 1.78, 95% CI 1.11-2.84, I2 = 0%) in the NRS. Recurrence rate was significantly lower in the PBT group compared with in up-front surgery group in the analysis of the RCT but not in NRS, (OR 0.34, 95% CI 0.13-0.91, I2 not applicable) and (OR 0.72, 95% CI 0.26-1.95, I2 = 51%) respectively. PBT was associated with a statistically significant lower rate of positive margins (OR 0.28, 95% CI 0.09-0.89; I2 = 42%) in the RCT and with a significantly higher rate of complete pathology response (CPR) in the RCT analysis (OR 2.55, 95% CI 1.11-5.85, I2 = 0%) and in the NRS (OR 9.64, 95% CI 1.88-49.48, I2 = 76%) compared with the up-front surgery group. CONCLUSION: Preoperative brachytherapy in patients with early-stage cervical cancer could improve pathologic and oncologic outcomes, but it should be assessed in high-quality randomized controlled trials before its implementation in clinical practice.

Morbidity of adjuvant treatment in early cervical cancer: a retrospective cohort study in a Latin American center.

Background: Radical hysterectomy with pelvic lymph node assessment is the standard of treatment in early cervical cancer. Adjuvant radiotherapy or chemoradiotherapy are offered to patients with risk factors for recurrence. The objective of this study was to compare the incidence of severe (> G3) early or late morbidity related to treatment in patients with cervical cancer undergoing radical surgery with/without adjuvant treatment in a Latin American center. Materials and methods: Retrospective cohort study of patients diagnosed with cervical cancer stage IA1 to IB1. Complications were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The cumulative incidence of severe morbidity was estimated. Risk ratios (RR) were calculated to determine the factors associated with morbidity. Results: 239 patients were included. 133 (55.6%) received only radical surgical management and 106 (44.4%) adjuvant treatment. The incidence of early morbidity was 18.8% [95% confidence interval (CI): 12.6% to 26.5%] in the group without adjuvant treatment versus 21.7% (95% CI: 14.3% to 30.8%) in the adjuvant treatment group (p = 0.58). Late morbidity was 3% (95% CI: 1% to 7.5%) and 8.5% (95% CI: 4% to 15.5%), respectively (p = 0.063). No statistically significant differences regarding grade ≥ 3 morbidity between the groups was found (2.3% vs. 5.7%, p = 0.289). Complications during surgery is the only factor associated with postoperative morbidity related to treatment (RR = 4.1) (95% CI: 3% to 5.7%). Conclusion: In our study, the addition of adjuvant treatment for early cervical cancer patients who underwent radical surgery did not increase the incidence of severe early or late morbidity.

PTH1R translocation to primary cilia in mechanically-stimulated ostecytes prevents osteoclast formation via regulation of CXCL5 and IL-6 secretion.

Osteocytes respond to mechanical forces controlling osteoblast and osteoclast function. Mechanical stimulation decreases osteocyte apoptosis and promotes bone formation. Primary cilia have been described as potential mechanosensors in bone cells. Certain osteogenic responses induced by fluid flow (FF) in vitro are decreased by primary cilia inhibition in MLO-Y4 osteocytes. The parathyroid hormone (PTH) receptor type 1 (PTH1R) modulates osteoblast, osteoclast, and osteocyte effects upon activation by PTH or PTH-related protein (PTHrP) in osteoblastic cells. Moreover, some actions of PTH1R seem to be triggered directly by mechanical stimulation. We hypothesize that PTH1R forms a signaling complex in the primary cilium that is essential for mechanotransduction in osteocytes and affects osteocyte-osteoclast communication. MLO-Y4 osteocytes were stimulated by FF or PTHrP (1-37). PTH1R and primary cilia signaling were abrogated using PTH1R or primary cilia specific siRNAs or inhibitors, respectively. Conditioned media obtained from mechanically- or PTHrP-stimulated MLO-Y4 cells inhibited the migration of preosteoclastic cells and osteoclast differentiation. Redistribution of PTH1R along the entire cilium was observed in mechanically stimulated MLO-Y4 osteocytic cells. Preincubation of MLO-Y4 cells with the Gli-1 antagonist, the adenylate cyclase inhibitor (SQ22536), or with the phospholipase C inhibitor (U73122), affected the migration of osteoclast precursors and osteoclastogenesis. Proteomic analysis and neutralizing experiments showed that FF and PTH1R activation control osteoclast function through the modulation of C-X-C Motif Chemokine Ligand 5 (CXCL5) and interleukin-6 (IL-6) secretion in osteocytes. These novel findings indicate that both primary cilium and PTH1R are necessary in osteocytes for proper communication with osteoclasts and show that mechanical stimulation inhibits osteoclast recruitment and differentiation through CXCL5, while PTH1R activation regulate these processes via IL-6.

Primary cilia mediate parathyroid hormone receptor type 1 osteogenic actions in osteocytes and osteoblasts via Gli activation.

Mechanical stimulation of primary cilia in osteocytes and osteoblasts has been proposed as a mechanism that participates in bone cell survival and skeletal remodeling. Among different signaling pathways stimulated by primary cilia, the hedgehog signaling pathway has been associated with the regulation of bone development. Parathyroid hormone (PTH)-related protein (PTHrP) signaling through PTH 1 receptor (PTH1R) also regulates bone cell survival and remodeling and has been associated with the hedgehog pathway during skeletal development. We hypothesize that primary cilia and PTH1R concomitantly regulate bone remodeling and cell survival and aim to describe the mechanisms that mediate these effects in osteocytes and osteoblasts. Colocalization of PTH1R with primary cilia was observed in control and PTHrP-stimulated MLO-Y4 osteocytic and MC3T3-E1 osteoblastic cells. Activation of PTH1R by PTHrP increased cell survival, osteoblast gene expression (osteocalcin, runt-related transcription factor 2, and bone alkaline phosphatase) and the expression of the hedgehog transcription factor Gli-1 in osteocytes and osteoblasts. These effects were abrogated by small interfering RNAs for the primary cilia protein IFT88 or by a primary cilia specific inhibitor (chloral hydrate). Preincubation of MLO-Y4 osteocytic and MC3T3-E1 osteoblastic cells with the Gli-1 antagonist GANT61 inhibited PTHrP prosurvival actions but did not affect PTHrP-induced overexpression of osteogenic genes. Mechanical stimulation by fluid flow increased the number of primary cilia-presenting cells in osteocytes and osteoblasts. We propose that PTH1R activation induces prosurvival actions via primary cilia- and Gli-1-dependent mechanism and modulates osteogenic responses via a primary cilia-dependent and Gli-1-independent pathway in osteocytes and osteoblasts.

Transversus Abdominis Plane Block versus Epidural Anesthesia for Pain Management Post-Caesarean Delivery: A Pilot Study.

Background: Effective post-operative analgesia profoundly influences patient recovery and outcomes after caesarean delivery. The Transversus Abdominis Plane (TAP) block represents a potential alternative, potentially offering greater effectiveness than epidural analgesia while causing fewer adverse effects. Objective: To assess if the abdominal transverse block provides superior postoperative pain relief in patients undergoing caesarean delivery compared to epidural analgesia. Methods: Participants were divided into parallel groups: an experimental group receiving TAP block (n=25) and a control group receiving epidural analgesia (n=24). All patients received a 10 mg dose of hyoscine at the end of the surgery. Experimental Group received a total of 20 mL of 0.2% ropivacaine. In Epidural group received 0.2% ropivacaine at 4 mL/h for 24 hours. All participants were administered combined with neuroaxial block anesthesia. The patients selected for epidural analgesia received the mentioned dose, while the other group block had the epidural catheter removed after the cesarean section. The primary outcome was post-caesarean pain, evaluated using the Visual Analog Scale (VAS) at four intervals (0, 6, 12, and 24 hours). Also, surgical bleeding and residual motor were evaluated. VAS pain scores between the groups were compared using the Friedman test and Generalized Linear Model (GLM) for non-normally distributed data. The effect size was estimated with Eta Square ([Formula: see text]), considering values ≥0.38 as indicative of large effects. A two-tailed p-value < 0.05 was deemed statistically significant. Results: Statistically significant differences in pain scores were noted at 0 and 6 hours post-surgery (p<0.01). The TAP block group reported lower pain scores at 0 hours (mean=0.04) and 6 hours (mean=1.16) compared to the epidural group, reflecting a substantial effect size. Conclusion: The TAP block proves advantageous in mitigating postoperative pain for women post-caesarean delivery, particularly in the initial 6 postpartum hours. This relief promotes early mother-infant bonding and facilitates breastfeeding.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Primary cilia and PTH1R interplay in the regulation of osteogenic actions.

Primary cilia are subcellular structures specialized in sensing different stimuli in a diversity of cell types. In bone, the primary cilium is involved in mechanical sensing and transduction of signals that regulate the behavior of mesenchymal osteoprogenitors, osteoblasts and osteocytes. To perform its functions, the primary cilium modulates a plethora of molecules including those stimulated by the parathyroid hormone (PTH) receptor type I (PTH1R), a master regulator of osteogenesis. Binding of the agonists PTH or PTH-related protein (PTHrP) to the PTH1R or direct agonist-independent stimulation of the receptor activate PTH1R signaling pathways. In turn, activation of PTH1R leads to regulation of bone formation and remodeling. Herein, we describe the structure, function and molecular partners of primary cilia in the context of bone, playing special attention to those signaling pathways that are mediated directly or indirectly by PTH1R in association with primary cilia during the process of osteogenesis.

A pilot study on the effect of Basic Body Awareness Therapy in patients with eating disorders: a randomized controlled trial.

OBJECTIVE: To analyse the feasibility of Basic Body Awareness Therapy in people with eating disorders. DESIGN: A randomized controlled trial; the assessors were not blinded to the group allocation. SETTING: The eating disorders department within a hospital setting. SUBJECTS: Twenty-eight outpatients with eating disorders for less than five years. INTERVENTION: All patients received standard outpatient treatment. The intervention group (n = 14) also received Basic Body Awareness Therapy for seven weeks. MAIN MEASURES: Eating Disorder Inventory, Eating Attitude Test, Body Attitude Test and Quality of Life Scale SF-36. RESULTS: Analysing the differences between both groups, significant differences were found in Eating Disorder Inventory (mean difference: 26.3; P = 0.015) and in its subscales 'drive to thinness' (P = 0.003), 'body dissatisfaction' (P = 0.025) and 'ineffectiveness' (P = 0.014). Also in Body Attitude Test (mean difference: 33.0; P = 0.012), Eating Attitude Test-40 (mean difference: 17.7; P = 0.039) and SF-36 in the section 'mental health' (mean difference: 13.0; P = 0.002). CONCLUSIONS: This study has shown some effectiveness of Basic Body Awareness Therapy in improving some symptoms in outpatients with eating disorders. Further studies should include larger samples, double-blinded and placebo methodologies, and should focus on questions such as which eating disorder diagnoses benefit most from physical therapy.

Systematic Review of Therapeutic Physical Exercise in Patients with Amyotrophic Lateral Sclerosis over Time.

BACKGROUND: the main objective of this study was to analyze the potential short-, medium- and long-term effects of a therapeutic physical exercise (TFE) programme on the functionality of amyotrophic lateral sclerosis (ALS) patients, measured with the Revised Amyotrophic Lateral Sclerosis Functional Scale (ALSFRS-R) scale. METHODS: a systematic review of the PubMed, SCOPUS, Cochrane, Scientific Electronic Library Online (Scielo), Physiotherapy Evidence Database (PEDro), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Medical Literature Analysis and Retrieval System Online (MEDline) databases was carried out. The information was filtered using the following Medical Subjects Heading (MeSH) terms: "Amyotrophic lateral sclerosis", "Physical Therapy", and "Physical and Rehabilitation Medicine". The internal validity of the selected documents was evaluated using the PEDro scale. The study included clinical trials published in the last 5 years in which one of the interventions was therapeutic physical exercise in patients with ALS, using the ALSFRS-R as the main outcome variable and functional variables as secondary variables. RESULTS: 10 clinical trials were analyzed, with an internal validity of 5-7 points. The TFE groups showed significant short-, medium- and long-term differences, obtaining a mean difference of 5.8 points compared to the 7.6 points obtained by the control groups, at six months, measured with ALSFRS-R. In addition, the participants showed significant improvements in functional abilities in the short, medium and long terms. CONCLUSIONS: Therapeutic physical exercise could contribute to slowing down the deterioration of the musculature of patients with ALS, thus facilitating their performance in activities of daily living, based on the significant differences shown by these individuals in the short, medium and long term both in subjective perception, measured with ALSFRS-R, and functional capacities.

Stabilization Exercises Versus Flexion Exercises in Degenerative Spondylolisthesis: A Randomized Controlled Trial.

OBJECTIVE: Exercise is the mainstay of treatment in individuals with low back pain and the first-line option in degenerative spondylolisthesis (DS); however, there is still no consensus surrounding the superiority of any specific exercise program. Thus, the primary aim of this study was to compare the effectiveness of lumbar stabilization exercises and flexion exercises for pain control and improvements of disability in individuals with chronic low back pain (CLBP) and DS. METHODS: A randomized controlled trial was conducted in a tertiary public hospital and included 92 individuals over the age of 50 years who were randomly allocated to lumbar stabilization exercises or flexion exercises. Participants received 6 sessions of physical therapy (monthly appointments) and were instructed to execute exercises daily at home during the 6 months of the study. The primary outcome (measured at baseline, 1 month, 3 months, and 6 months) was pain intensity (visual analog scale, 0-100 mm) and disability (Oswestry Disability Index, from 0% to 100%). Secondary outcomes were disability (Roland-Morris Disability Questionnaire, from 0 to 24 points), changes in body mass index, and flexibility (fingertip to floor, in centimeters) at baseline and 6 months, and also the total of days of analgesic use at 6-month follow-up. RESULTS: Mean differences between groups were not significant (for lumbar pain: 0.56 [95% CI = -11.48 to 12.61]; for radicular pain: -1.23 [95% CI = -14.11 to 11.64]; for Oswestry Disability Index: -0.61 [95% CI = -6.92 to 5.69]; for Roland-Morris Disability Questionnaire: 0.53 [95% CI = -1.69 to 2.76]). CONCLUSION: The findings from the present study reveal that flexion exercises are not inferior to and offer a similar response to stabilization exercises for the control of pain and improvements of disability in individuals with CLBP and DS. IMPACT: Exercise is the mainstay of treatment in individuals with CLBP and DS; however, there is still no consensus surrounding the superiority of any specific exercise program. This study finds that flexion exercises are not inferior to and offer a similar response to stabilization exercises. LAY SUMMARY: Exercise is the mainstay of treatment in individuals with CLBP and DS, but there is no consensus on the superiority of any specific exercise program. If you have DS, flexion exercises may provide similar effects to stabilization exercises.

Alternative management for gynecological cancer care during the COVID-2019 pandemic: A Latin American survey.

OBJECTIVE: To determine the acceptance rate of treatment alternatives for women with either preinvasive conditions or gynecologic cancers during the COVID-19 pandemic among Latin American gynecological cancer specialists. METHODS: Twelve experts in gynecological cancer designed an electronic survey, according to recommendations from international societies, using an online platform. The survey included 22 questions on five topics: consultation care, preinvasive cervical pathology, and cervical, ovarian, and endometrial cancer. The questionnaire was distributed to 1052 specialists in 14 Latin American countries. A descriptive analysis was carried out using statistical software. RESULTS: A total of 610 responses were received, for an overall response rate of 58.0%. Respondents favored offering teleconsultation as triage for post-cancer treatment follow-up (94.6%), neoadjuvant chemotherapy in advanced stage epithelial ovarian cancer (95.6%), and total hysterectomy with bilateral salpingo-oophorectomy and defining adjuvant treatment with histopathological features in early stage endometrial cancer (85.4%). Other questions showed agreement rates of over 64%, except for review of pathology results in person and use of upfront concurrent chemoradiation for early stage cervical cancer (disagreement 56.4% and 58.9%, respectively). CONCLUSION: Latin American specialists accepted some alternative management strategies for gynecological cancer care during the COVID-19 pandemic, which may reflect the region's particularities. The COVID-19 pandemic led Latin American specialists to accept alternative management strategies for gynecological cancer care, especially regarding surgical decisions.

Análise da prática endodôntica realizada em clínicas odontológicas em uma cidade do Sul do Brasil / Analysis of endodontic practices in dental clinics in a Southern Brazilian city

Introdução: O desenvolvimento de novas técnicas, tecnologias e materiais influenciam a prática clínica da endodontia e impactam consideravelmente a forma como o tratamento do canal radicular é realizado. Embora existam informações sobre as várias formas de tratamentos praticados por dentistas em outras cidades e/ou países, muito pouco se sabe sobre as endodontias realizadas em clínicas odontológicas na cidade de Porto Alegre/RS. Objetivo: Analisar a prática endodôntica realizada por dentistas nas clínicas odontológicas na cidade de Porto Alegre/RS, visando explorar as técnicas, materiais e equipamentos empregados durante o tratamento. Material e método: Foi aplicado um questionário online, por meio da Plataforma Google Forms, com vinte e seis questões abertas e fechadas aos dentistas que realizam tratamentos endodônticos em clínicas odontológicas. O questionário foi estruturado a fim de analisar os materiais, técnicas e equipamentos que estão presentes nos tratamentos endodônticos realizados pelos dentistas nas clínicas odontológicas aqui avaliadas. Os dados coletados nos questionários foram transferidos para uma planilha Excel®. A análise dos dados foi feita de duas formas: frequência absoluta e relativa para as questões fechadas, e descritiva para as questões abertas. Resultado: 15,57% das clínicas odontológicas registradas no CRO/RS participaram da presente pesquisa. Foi possível verificar que a maioria dos materiais e técnicas aplicadas no tratamento endodôntico são os mesmos recomendados pela literatura científica. Conclusão: Os protocolos clínicos em endodontia seguidos pelos participantes do presente estudo apresentam embasamento clínico e científico na literatura.

Introduction: The evolution of new techniques, technologies, and materials significantly influences the clinical practice of endodontics, thus profoundly impacting the approach to root canal treatments. While information about various treatment methods practiced by dentists in other cities or countries is available, there is a notable gap in our understanding of endodontic practices in the Porto Alegre city. Objective: The objective of this study is to analyze the endodontic practices employed by dentists in dental clinics located in Porto Alegre city. We aimed to explore the techniques, materials, and equipment routinely utilized during endodontic treatments. Material and method: An online questionnaire using the Google Forms platform was administered, consisting of twenty-six open and closed questions to dentists performing endodontic treatments in dental clinics. The questionnaire was structured to assess the materials, techniques, and equipment employed during endodontic procedures. Data collected from the questionnaires were recorded in an Excel® spreadsheet. Data analysis encompassed both absolute and relative frequency for closed questions and also a descriptive approach for open-ended questions. Results: Participation was obtained from 15.57% of dental clinics registered with CRO/RS. The findings indicated that the majority of materials and techniques applied in endodontic treatment could be aligned with recommendations found in the scientific literature. Conclusion: The clinical protocols observed by the participants in endodontic practice demonstrated a solid foundation in both clinical and scientific literature.

Implicación de las conexinas, integrinas y cilio primario en la actividad de las células óseas / Involvement of connexins, integrins and primary cilium in the activity of bone cells

Introducción: los osteocitos son capaces de detectar diferentes señales, transducirlas en respuestas biológicas y trasmitirlasa los osteoblastos y osteoclastos, permitiendo el mantenimiento de la homeostasis ósea. La mecanotransducción ósea esposible gracias a que los osteocitos presentan diferentes estructuras mecanosensoras como las conexinas (Cx), las integrinas,el cilio primario e incluso receptores acoplados a proteínas G como el receptor de la parathormona tipo 1 (PTH1R).Objetivo: analizar la posible interacción de los diferentes elementos mecanosensores de los osteocitos y ver su influen-cia en la respuesta biológica.Material y métodos: se trabajó con las líneas celulares osteocíticas MLO-Y4 Cx43+/+ (scrambled (SCR) y ARNi α2) yCx43-/-.Resultados y conclusión: los resultados obtenidos muestran que la Cx43 y la integrina α2 se encuentran involucradas enel aumento de la longitud del cilio primario, afectando potencialmente a su funcionalidad como mecanosensor (SCR vs.ARNi α2, p < 0,0001 SCR vs. Cx43-/- y p < 0,0001 ARNi α2 vs. Cx43-/-). La integrina α2 también influyó en la localizacióncelular de Cx43 promoviendo que esta se encuentre en la membrana plasmática. También se observó que la activación dePTH1R por agonistas como parathormona (PTH) y proteína relacionada con la parathormona (PTHrP) inducen la fosforilaciónde la quinasa ERK 1/2, y estos efectos podrían verse afectados por la deficiencia en Cx43, pero no parecen ser mediadospor el silenciamiento de integrina α2. Finalmente, se observó que la presencia de la Cx43 y de integrina α2 en los osteoci-tos aumenta su capacidad de adhesión (Cx43+/+ SCR y ARNi α2 vs. CX43-/- p < 0,001 y p = 0,0039) y que la deficienciaen Cx43 provoca un incremento de la mortalidad de estas células (Cx43-/- vs. Cx43+/+ p = 0,0074).(AU)

Displasia mesenquimal placentaria asociada con restricción del crecimiento intrauterino de inicio temprano: reporte de un caso / Placental mesenchymal dysplasia associated with early onset intrauterine growth restriction: a case report

Resumen ANTECEDENTES: La displasia mesenquimal placentaria es una anomalía de la vasculatura y del tejido conectivo placentario que altera la estructura y la función de las vellosidades, se asocia con un desenlace perinatal adverso. CASO CLÍNICO: Paciente de 21 años, primigesta, con 15.2 semanas de embarazo establecidas por fetometría, con placenta corporal anterior, de morfología anormal, con múltiples imágenes hipoecogénicas que semejan racimos de uvas, sin flujo vascular en el Doppler color. La valoración ecográfica de las 33 semanas reportó fetometría para 27.2 semanas, anhidramnios y placentomagelia, con alteración en los parámetros de la flujometría Doppler. En la prueba sin estrés se diagnosticó restricción del crecimiento intrauterino estadio IV. La imagen del feto fue heterogénea en el flanco derecho de 4.7 x 4.1 cm. El embarazo finalizó por cesárea con una recién nacida con Apgar 8-9, de 930 gramos, placenta agrandada con vellosidades hidrópicas. El estudio histopatológico reportó: displasia mesenquimal placentaria. La resección del tumor abdominal fue electiva, por vía laparoscópica, al cuarto mes de vida, con diagnóstico histopatológico de hamartoma mesenquimal hepático. CONCLUSIÓN: La displasia mesenquimal placentaria es una anomalía placentaria benigna, relacionada con restricción del crecimiento intrauterino de inicio temprano que puede evolucionar, incluso, a la muerte del feto por hipoxia crónica debido a las anomalías en la vasculatura microscópica que afectan el desarrollo de las vellosidades terminales e interfiere en el intercambio de gases, nutrientes y electrolitos en el espacio intervelloso.

Abstract BACKGROUND: Placental mesenchymal dysplasia is an anomaly of the vasculature and placental connective tissue which alters the structure and function of the villi, being associated with an adverse perinatal outcome. CLINICAL CASE: Patient 21 years old, primigestation, with 15.2 weeks of pregnancy established by fetometry, with anterior body placenta, abnormal morphology, with multiple hypoechogenic images resembling clusters of grapes, without vascular flow in color Doppler. Ultrasound evaluation at 33 weeks, reporting fetometry for 27.2 weeks, anhydramnios and placentomagelia, with alteration in Doppler parameters, as well as in a non-stress test diagnosing fetal growth restriction stage IV. Fetus with heterogeneous image on the right flank of 4.7 x 4.1 cm. Abdominal pregnancy interruption was decided, obtaining a live female newborn, Apgar 8/9, weight 930 grams, enlarged placenta with hydropic villi. The histopathology study reports placental mesenchymal dysplasia. Abdominal tumor resection was performed electively by laparoscopy at 4 months of age with a histopathological diagnosis of hepatic mesenchymal hamartoma. CONCLUSION: Placental mesenchymal dysplasia is a benign placental anomaly, related to early-onset intrauterine growth restriction that can even progress to fetal death by chronic hypoxia due to abnormalities in the microscopic vasculature that affect the development of the terminal villi and interfere with the exchange of gases, nutrients and electrolytes in the intervillous space.

The role of stereotactic ablative radiotherapy (SBRT) in the management of oligometastatic non small cell lung cancer.

Our understanding of metastatic disease has evolved significantly in the last 20 years. Considered strictly a systemic issue, local treatment would only have significant impact in terms of palliation. However, Hellman and Weichselbaum stated that there might be an intermediate state, in which controlling limited metastatic sites could improve oncologic outcomes. This is called an oligometastatic state, a point between locally confined cancer and widespread disease [1,2]. As treatment with chemotherapy alone for non small cell lung cancer (NSCLC) yields median survivals of 8-11 months [3] and minimal chances of long term survival, new strategies are needed to offer better odds for metastatic patients. Outcomes tend to be better in patients with low volume metastatic disease. [4,5], leading us to question whether the oligometastatic group of patients will gain from a more radical treatment paradigm. In this setting, ablative treatments like surgery or SBRT may provide longer survival and better local control times. There is a rationale for the use of ablative local treatments, as most failures after chemotherapy occur at sites initially affected by disease, and these sites could be a source of further dissemination. Also, chemotherapy resistance can adversely impact resolution of metastatic disease [6]. In rare cases, the abscopal effect (an immune effect arising after radiotherapy in non irradiated metastatic sites) has been described [7,8]. In this review article, we address the impact of SBRT in oligometastatic NSCLC, the most relevant prognostic factors, indications and a site specific review. This review will focus on SBRT for extracranial disease as the role for intracranial SBRT is established.