Pneumothorax, Pneumomediastinum, and Cervical and Facial Massive Emphysema Secondary to Colonoscopy: A Rare Complication of Colonoscopy.

Background: Colonoscopy is a resource used for the diagnosis, treatment, and monitoring of benign and malignant colorectal pathologies. The incidence of perforation is 0.03%-0.65% in diagnostic colonoscopy; however, the incidence can be up to 10 times higher in therapeutic interventions, such as polypectomies, increasing the risk of complications up to 0.07-2.1%. Materials and methods. Case report of a 71-year-old female who presents a rare complication due to a perforation in the sigmoid which developed pneumoperitoneum, pneumomediastinum, pneumothorax, and massive subcutaneous emphysema as a complication of a diagnostic colonoscopy where a biopsy of a friable lesion was performed. Results: A 71-year-old female that went to the emergency room due to acute generalized abdominal colic spasm pain with a duration of 7 hours, associated with significant abdominal distension, malaise, diaphoresis, progressive dyspnea, and massive subcutaneous emphysema that developed after performing panendoscopy and colonoscopy for diverticulosis follow-up. An abdominal CT scan with double contrast was performed, reporting suggestive data of hollow viscus perforation, pneumoperitoneum, pneumomediastinum, pneumothorax, and massive subcutaneous emphysema in the thorax, neck, and skull base. She underwent an exploratory laparotomy finding a perforation in the sigmoid for which sigmoidectomy was performed, and for the pneumothorax and pneumomediastinum, endopleural tubes were placed in both hemithoraxes. The massive subcutaneous emphysema subsided with observation and oxygen. Conclusion: A rare complication of the use of colonoscopy as a diagnostic and therapeutic method is presented. The purpose of presenting this case is for the doctor who performs these interventions to suspect this complication in a timely manner, not delaying the diagnosis and carrying out an urgent therapeutic approach as in this case with exploratory laparotomy, finding the perforation site and carrying out the corresponding surgical management. We demonstrated that massive subcutaneous emphysema can be managed with observation if there is no other alarm data evident that required another surgical approach.

Chronic Encapsulated Sclerosing Peritonitis: A Case Report.

Chronic encapsulated sclerosing peritonitis (CESP) is a very rare cause of intestinal obstruction that has been associated with certain chronic conditions. It is characterized by the thickening of the peritoneum, generating a membrane that covers the intestinal loops and prevents their adequate mobilization. Most cases present as a surgical emergency, leading to a diagnosis during surgery; however, imaging studies can support the pre-surgical diagnosis. Treatment is based on the clinical context of the patient, based on medical management with corticosteroids in a stable patient, or surgical management when it presents as an acute complication. The morbidity and mortality associated with this condition are high and epidemiological data are scarce. There is still a lack of studies to describe the associated demographic data, diagnosis, and treatment.

Randomized Phase III Trial Evaluating Subcutaneous Rituximab for the First-Line Treatment of Low-Tumor Burden Follicular Lymphoma: Results of a LYSA Study.

PURPOSE: Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden follicular lymphoma (FL). Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low-tumor burden FL. METHODS: Patients with histologically confirmed CD20+ low-tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m2 once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m2, on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS). RESULTS: Two hundred two patients with low-tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 [0.393 to 0.871]; P = .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm (P = .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT. CONCLUSION: SC rituximab improves PFS for patients with low-tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.

Hallazgos ultrasonográficos y laparoscópicos en pacientes con endometriosis profunda

Objetivo: Determinar los hallazgos ultrasonográficos y laparoscópicos en pacientes con endometriosis profunda en el Servicio de Ginecología del Complejo Hospitalario Dr. Arnulfo Arias Madrid, Caja de Seguro Social (CHMDAAM - CSS). Metodología: Estudio descriptivo observacional transversal retrospectivo donde se evaluaron mediante expedientes clínicos los hallazgos ultrasonográficos y laparoscópicos en 48 pacientes con endometriosis en el servicio de Ginecología del Complejo Hospitalario Dr. Arnulfo Arias Madrid. Resultados: La prevalencia de endometriosis fue mayor en el grupo etario de 31 a 40 años (58%). La mayoría de la sintomatología presentada fue en el grupo de 31 a 40 años. Siendo la dismenorrea el síntoma más frecuente. En los hallazgos ultrasonográficos, la mayoría se encontró en el comportamiento posterior, involucrando mayormente al recto. Los hallazgos laparoscópicos más frecuentes fueron en el comportamiento posterior. En nuestro estudio, 35 de 46 de las pacientes con hallazgos ultrasonográficos que demostraba endometriosis profunda, tenían en la laparoscopia endometriosis profunda. Es decir, el ultrasonido por mapeo de endometriosis fue capaz de predecir el 76% de los hallazgos por laparoscopia. Conclusiones: los hallazgos ultrasonográficos concuerdan en su mayoría con los hallazgos encontrados por laparoscopia, siendo el compartimiento posterior el más afectado, las lesiones en el recto fueron las más frecuentes encontradas. (provisto por Infomedic International)

Objective: To determine the ultrasonographic and laparoscopic findings in patients with deep endometriosis in the Gynecology Service of the Dr. Arnulfo Arias Madrid Hospital Complex, Caja de Seguro Social (CHMDAAM - CSS). Methodology: Retrospective cross-sectional observational descriptive study in which ultrasonographic and laparoscopic findings in 48 patients with endometriosis in the Gynecology Service of the Complejo Hospitalario Dr. Arnulfo Arias Madrid were evaluated by means of clinical records. Results: The prevalence of endometriosis was higher in the 31-40 years age group (58%). Most of the symptomatology presented was in the 31 to 40 years age group. Dysmenorrhea was the most frequent symptom. In the ultrasonographic findings, most were found in the posterior behavior, mostly involving the rectum. The most frequent laparoscopic findings were in the posterior behavior. In our study, 35 of 46 of the patients with ultrasonographic findings demonstrating deep endometriosis had deep endometriosis at laparoscopy. In other words, endometriosis mapping ultrasound was able to predict 76% of the laparoscopic findings. Conclusions: the ultrasonographic findings are mostly consistent with the findings found by laparoscopy, being the posterior compartment the most affected, lesions in the rectum were the most frequently found. (provided by Infomedic International)

Single cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.

Normal hematopoiesis requires constant prolific production of different blood cell lineages by multipotent hematopoietic stem cells (HSC). Stem- and progenitor- cells need to balance dormancy with proliferation. How genetic alterations impact frequency, lineage potential, and metabolism of HSC is largely unknown. Here, we compared induced expression of KRAS G12D or RasGRP1 to normal hematopoiesis. At low-resolution, both Ras pathway lesions result in skewing towards myeloid lineages. Single-cell resolution CyTOF proteomics unmasked an expansion of HSC- and progenitor- compartments for RasGRP1, contrasted by a depletion for KRAS G12D . SCENITH™ quantitates protein synthesis with single-cell precision and corroborated that immature cells display low metabolic SCENITH™ rates. Both RasGRP1 and KRAS G12D elevated mean SCENITH™ signals in immature cells. However, RasGRP1-overexpressing stem cells retain a metabolically quiescent cell-fraction, whereas this fraction diminishes for KRAS G12D . Our temporal single cell proteomics and metabolomics datasets provide a resource of mechanistic insights into altered hematopoiesis at single cell resolution.

Diagnóstico prenatal de enfermedad de canal atrio-ventricular, análisis epidemiológico y experiencia CERPO entre 2003 y 2021 / Prenatal diagnosis of atrio-ventricular canal disease, epidemiological analysis and CERPO experience between 2003 and 2021

Antecedentes: En Chile, la mitad de los casos de mortalidad perinatal son atribuibles a anomalías congénitas, y un tercio de estas corresponde a cardiopatías congénitas. Aproximadamente un 35% de estos últimos requerirán cirugía antes del año de vida, por lo que la pesquisa prenatal impacta profundamente en el pronóstico. Objetivo: Dar a conocer los resultados perinatales de pacientes con diagnóstico prenatal de canal atrio-ventricular controlados en el Centro de Referencia Perinatal Oriente (CERPO) entre los años 2003 y 2021, su asociación a otras anomalías, características demográficas y pronóstico a un año. Métodos: En este estudio se puede apreciar que tanto el pronóstico como el plan terapéutico posnatal dependerán de la presencia de otras alteraciones morfológicas y del estudio genético. De los factores estudiados, se puede concluir que tanto la presencia de anomalías cardiacas asociadas, como el grado de insuficiencia valvular y el tipo de canal no son predictores de la sobrevida perinatal. Conclusiones: Finalmente, en relación con la sobrevida posnatal, en este estudio, la sobrevida a un año de los recién nacidos vivos fue de un 52%, pero al desglosarlo en los niños con cariotipo euploide y trisomía 21, estos valores se tornan muy distintos, 44 y 81% respectivamente.

Background: In Chile, half of the perinatal mortality cases are attributable to congenital anomalies, and one third of these correspond to congenital heart disease. Approximately 35% of the later will require surgery before one year of life, so prenatal screening has a profound impact on the prognosis. Objective: To present the perinatal results of patients with a prenatal diagnosis of atrio-ventricular canal controlled at Centro de Referencia Perinatal Oriente CERPO) between 2003 and 2021, its association with other anomalies, demographic characteristics, and 1-year prognosis. Methods: In this study it can be seen that both the prognosis and the postnatal therapeutic plan will depend on the presence of other morphological alterations and the genetic study. From the factors studied, it can be concluded that the presence of associated cardiac anomalies, the degree of valvular insufficiency, and the type of canal are not predictors of perinatal survival. Conclusions: Finally, in relation to postnatal survival, in this study, the 1-year survival of live newborns was 52%, but when broken down into children with euploid karyotype and trisomy 21, these values become very different, 44 and 81% respectively.

Cellular architecture of human brain metastases.

Brain metastasis (BrM) is the most common form of brain cancer, characterized by neurologic disability and an abysmal prognosis. Unfortunately, our understanding of the biology underlying human BrMs remains rudimentary. Here, we present an integrative analysis of >100,000 malignant and non-malignant cells from 15 human parenchymal BrMs, generated by single-cell transcriptomics, mass cytometry, and complemented with mouse model- and in silico approaches. We interrogated the composition of BrM niches, molecularly defined the blood-tumor interface, and revealed stromal immunosuppressive states enriched with infiltrated T cells and macrophages. Specific single-cell interrogation of metastatic tumor cells provides a framework of 8 functional cell programs that coexist or anticorrelate. Collectively, these programs delineate two functional BrM archetypes, one proliferative and the other inflammatory, that are evidently shaped through tumor-immune interactions. Our resource provides a foundation to understand the molecular basis of BrM in patients with tumor cell-intrinsic and host environmental traits.

El día después: comportamientos de riesgo y protección ante el COVID-19 durante los comienzos de la cuarentena / The day after: risk and protection behaviours towards COVID-19 during the early quarantine

La declaración de la pandemia (Organización Mundial de la Salud, OMS, 2020) causada por el COVID-19 ha generado, a nivel global y en tiempo récord, investigaciones y publicaciones de evidencias preliminares. En este contexto, dentro de un diseño exploratorio, correlacional y comparativo, de corte transversal, se indaga comportamientos de riesgo y de protección (resiliencia, autoeficacia y afrontamiento) ante el COVID 19, percibidos individual y colectivamente, por los encuestados durante y post cuarentena. Participaron 1.134 encuestados, 31.48% hombres y 68.52% mujeres, con edad promedio de 30.18 años, el 94.4% residentes de Paraguay. Se destaca el acatamiento de normas de bioseguridad por parte de los participantes en el distanciamiento físico (62,17%), lavado regular de manos (89,8%), uso de tapabocas (81,13%). Existe acuerdo en la efectividad de la cuarentena para frenar el contagio (92,86%), pero una baja percepción de la capacidad para manejar el estrés individual en aislamiento (m=1.88; ds= .83), baja recurrencia a profesionales de la salud por ayuda (m= .86; s= 1.02), y un bajo nivel de afrontamiento en comparación a los otros factores preventivos (m= 10.61; ds=3.25). Importante seguir esta línea de investigación para las fases de confinamiento en proceso.

The declaration of the pandemic (WHO, 2020) caused by COVID-19 has generated, at a global level and in record time, investigations and publications of preliminary evidence. In this context, risk and protective behaviours (resilience, self-efficacy and coping) were investigated, perceived individually and collectively, by respondents during and after lockdown within an exploratory, correlational, and comparative, crosssectional design. The survey considered 1,134 respondents, with 31.48% men and 68.52% women, the average age was 30.18 years, and 94.4% were Paraguay residents. The study highlights the observance of biosafety regulations by the participants in terms of physical distance (62.17%), regular handwashing (89.8%) and use of face masks (81.13%). There is agreement on the effectiveness of lockdown to stop contagion (92.86%), but a low perception of the ability to handle individual stress in isolation (m = 1.88; ds = .83), low recurrence to health professionals for help (m = .86; s = 1.02), and a low level of coping compared to the other preventive factors (m = 10.61; ds = 3.25). It is important to follow this investigation line for the current lockdown phases.

Utilidad del apósito liofilizado de piel de cerdo en el manejo de cicatrización de úlcera de pie diabético / Usefulness of lyophilized pig skin dressings in wound healing as treatment for diabetic foot ulcer

Resumen Objetivo: Mostrar la utilidad del apósito liofilizado de piel de cerdo comparado con el manejo conservador con sulfadiazina de plata en el proceso de cicatrización de la úlcera de pie diabético. Materiales y Método: Estudio cuasiexperimental en pacientes con diagnóstico de pie diabético, se establecieron 2 grupos de estudio utilizando una relación 2:1, el grupo de exposición (10 pacientes) tratado con apósito liofilizado de piel de cerdo y el grupo de control (5 pacientes) manejado con sulfadiazina de plata. La utilidad se midió con la cicatrización en semanas de tratamiento. El análisis estadístico incluyó prueba de t, prueba de z, regresión logística simple y cálculo de la probabilidad del evento. Resultados: El tiempo de cicatrización fue más corto en el grupo manejado con apósito liofilizado de piel de cerdo (10,20 semanas) que en el grupo con manejo a base de sulfadiazina de plata (13,8 semanas). A las 9 semanas de iniciado el tratamiento, la mitad de las pacientes con apósito de piel de cerdo ya habían cicatrizado comparado con la cicatrización en el grupo manejado con sulfadiazina de plata (20%). La probabilidad de cicatrización a las 11 semanas en paciente manejados con sulfadiazina de plata es 20% y con apósito liofilizado de piel de cerdo 80%. Conclusión: El apósito liofilizado de piel de cerdo tuvo mejores resultados en el estudio, comparado con el manejo estándar con sulfadiazina de plata. Es necesario realizar un estudio aleatorizado para determinar la efectividad de este material como herramienta terapéutica.

Aim: To demonstrate the usefulness of lyophilized pig skin dressings versus usual management with silver sulfadiazine in wound healing treatment for diabetic foot ulcers. Materials and Method: In this quasi-experimental study, we included patients diagnosed with diabetic foot. We established two groups with a distribution (2:1), the exposure group treated with lyophilized pig skin dressings (10 patients) and the control group (5 patients), the standard of care with silver sulfadiazine. Usefulness was measured with wound healing in treatment weeks. Statistical analysis included t-test, z-test, simple logistic regression, and calculation of probability of an event. Results: Wound healing time was shorter in the group treated with lyophilized pig skin dressing (10.20 weeks) than in the group treated with silver sulfadiazine (13.8 weeks). At 9 weeks after treatment started, 50% of patients treated with lyophilized pig skin dressings had complete wound healing compared with the patients in the group managed with silver sulfadiazine. (20%). The probability of wound healing been completed at 11 weeks in a patient managed with silver sulfadiazine is 20%, compared to lyophilized pig skin dressings is 80%. Conclusion: Lyophilized pig skin dressings had better outcomes than silver sulfadiazine in wound healing treatment for diabetic foot ulcers inside the study. Is mandatory develop another study with a randomized design to determinate the effectiveness as a therapeutic alternative.

Gastrointestinal hemorrhage as the first manifestation of metastatic choriocarcinoma in a male patient.

INTRODUCTION: Choriocarcinoma is a malignant tumor, it is more frequent in the female sex, rarely reported in the male sex. CLINICAL CASE: A 19-year-old male patient who was admitted with hematochezia and melenic evacuations, panendoscopy and colonoscopy were performed without documenting the bleeding site, exploratory laparotomy was performed finding tumor lesion in the jejunum, the histopathological examination reported Choriocarcinoma. CONCLUSIONS: Gastrointestinal bleeding as a presentation of choriocarcinoma is sometimes the only symptom that the patient presents. Metastatic choriocarcinoma to the gastrointestinal tract is rare, which makes the suspected diagnosis poor.

INTRODUCCIÓN: El coriocarcinoma es un tumor maligno, más frecuente en el sexo femenino, raramente reportado en el sexo masculino. CASO CLÍNICO: Varón de 19 años que ingresa con hematoquecia y evacuaciones melénicas. Se realiza panendoscopia y colonoscopia, sin documentar el sitio de sangrado. Se realiza laparotomía exploradora y se encuentra una lesión tumoral en el yeyuno, cuyo examen histopatológico reportó coriocarcinoma. CONCLUSIONES: La hemorragia de tubo digestivo como presentación de un coriocarcinoma es en ocasiones el único síntoma que muestra un paciente. El coriocarcinoma metastásico al tracto gastrointestinal es raro, lo que hace que la sospecha diagnóstica sea pobre.

Mental health problems among healthcare workers involved with the COVID-19 outbreak

Objective: The mental health problems and perceived needs of healthcare workers involved with coronavirus disease (COVID-19) may vary due to individual and contextual characteristics. The objective of this study was to evaluate healthcare workers' mental health problems during the common COVID-19 exposure scenario in Mexico, comparing those on the frontline with other healthcare workers according to gender and profession, determining the main risk factors for the most frequent mental health problems. Methods: A cross-sectional online study was conducted with a non-probabilistic sample of 5,938 Mexican healthcare workers who completed brief screening measures of mental health problems and ad hoc questions about sociodemographic professional characteristics, conditions related to increased risk of COVID-19 infection, life stressors during the COVID-19 emergency, and perceived need to cope with COVID-19. Results: The identified mental health problems were insomnia, depression, and posttraumatic stress disorder (PTSD), all of which were more frequent in frontline healthcare workers (52.1, 37.7, and 37.5%, respectively) and women (47.1, 33.0 %, and 16.3%, respectively). A lack of rest time was the main risk factor for insomnia (OR = 3.1, 95%CI 2.6-3.7, p ≤ 0.0001). Mourning the death of friends or loved ones due to COVID-19 was the main risk factor for depression (OR = 2.2, 95%CI 1.8-2.7, p ≤ 0.0001), and personal COVID-19 status was the main risk factor for PTSD (OR = 2.2, 95%CI 1.7-2.9, p ≤ 0.0001). Conclusion: The most frequent mental health problems during the common exposure scenario for COVID-19 in Mexico included the short-term psychological consequences of intense adversity. A comprehensive strategy for preventing mental health problems should focus on individuals with cumulative vulnerability and specific risk factors.

Características morfofuncionales de una muestra de futbolistas profesionales chilenos de primera B según posición de juego / Morfofunctional Characteristics of a Sample From First B Chilean Professional Football Players According to Playing Position

Resumen Objetivo: analizar el perfil morfofuncional de futbolistas profesionales chilenos según su posición de juego. Método: el diseño del estudio fue no experimental, con un alcance descriptivo-correlacional. Se evaluaron 29 futbolistas profesionales de la primera B. Para determinar el porcentaje graso se midieron cuatro pliegues cutáneos y se aplicó la ecuación de Durnin y Womersley; para las variables físicas se aplicó el test de 1 repetición máxima de sentadillas y se utilizó el método de Brzycki para proyectar la fuerza máxima; en fuerza explosiva se ejecutó el Test de Bosco que evalúa el salto Squat Jump (SJ); para la resistencia aeróbica se utilizó el Yoyo test nivel 1 de recuperación, con toma de frecuencia cardiaca (FC) al final y en recuperación (1 minuto). Resultados: se observan solo diferencias significativas en la talla entre arqueros y volantes (F=4.491; p=0.012), esto implica, que la edad, peso y Σ4 pliegues no inciden en la posición de juego. Conclusiones: se observa que, en cada posición de juego, los jugadores presentan una configuración morfofuncional distinta, lo cual permite inferir que el trabajo debe ser diferenciado.

Abstract Objective: to analyze the morphofunctional profile of Chilean professional soccer players according to their playing position. Method: the study design was non-experimental, with a descriptive-correlational scope. Twenty-nine professional soccer players belonging to the Valdivia Sports Club of Chile were evaluated. Fat percentage was established by measuring four skin folds and applying the Durnin and Womersley equation. For the physical variables, the maximum squat repetition test was applied, and the Brzycki method was used to project the maximum force in one repetition. In explosive force, the Bosco Test was performed; this test evaluates the squat jump (SJ). The level 1 recovery Yoyo Test was used for the aerobic resistance, with heart rate (HR) measurement at the end and in recovery (1 minute). Results: Only significant differences in height are observed between goalkeepers and midfielders (F =4.491;p= 0.012); this implies that age, weight, and Σ4 folds do not affect in the playing position. Conclusions: it is observed that, in each game position, the players present a different morphofunctional configuration, which allows inferring that the work must be differentiated.

Resumo Objetivo: analisar o perfil morfofuncional de jogadores profissionais chilenos de futebol segundo sua posição de jogo. Método: o desenho do estudo foi não experimental, de escopo descritivo-correlacional. Foram avaliados 29 jogadores de futebol profissional do primeiro B. Para determinar o percentual de gordura, foram medidas quatro dobras cutâneas e aplicada a equação de Durnin e Womersley; Para as variáveis físicas foi aplicado o teste de 1 repetição máxima de agachamento e utilizado o método de Brzycki para projetar a força máxima; Na força explosiva, foi realizado o Teste de Bosco, que avalia o Salto de Agachamento (SJ); Para a resistência aeróbia, foi utilizado o teste de recuperação Yoyo nível 1, com frequência cardíaca (FC) medida no final e na recuperação (1 minuto). Resultados: foram observadas apenas diferenças significativas na altura entre goleiros e petecas (F = 4,491; p = 0,012), isso implica que idade, peso e Σ4 dobras não interferem na posição de jogo. Conclusões: observa-se que, em cada posição de jogo, os jogadores apresentam uma configuração morfofuncional diferente, o que permite inferir que o trabalho deve ser diferenciado.

GIST associated with von recklinghausen disease: Report of two cases and review of literature.

INTRODUCTION AND IMPORTANCE: Neurofibromatosis type 1 (NF1), or Von Recklinghausen's disease, is an autosomal dominant condition that affects the central nervous system. Gastrointestinal stromal tumor (GIST) refers to non-epithelial tumors of the gastrointestinal tract lacking smooth muscle structural features and schwann cell immunohistochemical characteristics. The risk of patients with NF1 to develop a GIST is 7%. CASE PRESENTATION: GIST is a soft tissue sarcoma that probably arises from the interstitial Cajal cells of the intestine. GIST associated with NF1 syndrome appears to have a distinct phenotype, occurring in younger patients compared to sporadic GIST. CLINICAL DISCUSSION: The clinical presentation can be highly variable, the association of gastrointestinal tumors associated with Von Recklinghausen's disease is up to 7%, postoperative treatment with imatinib is reserved for patients with a high risk of recurrence. CONCLUSION: The treatment of primary GIST is complete surgical resection with free microscopic margins and an intact pseudocapsule.

The CYP707A Gene Family in Strawberry (Fragaria × ananassa)

Abstract Abscisic acid (ABA) is a plant hormone that plays several roles in plant development. The de novo synthesis and the reversible inactivation of ABA have been largely described in the literature; however, the degradation of ABA, promoted by the enzymes Abscisic Acid 8'-Hydroxylase, encoded by the CYP707A gene family, is still poorly elucidated. Strawberry (Fragaria x ananassa) has been used as a model to study the ABA-dependent maturation process of non-climacteric fruits, and the ABA-dependent response to abiotic stress. However, the CYP707A genes from this species have not been fully described and characterized. In this perspective, FaCYP707A sequences were identified from strawberry fruit transcriptome and several structural and comparative genomic analyzes were performed. Moreover, the expression of the FaCYP707A sequences identified was investigated in fruits under salt stress and ABA application. Four putative FaCYP707A were identified and the structural analysis confirmed the identity of three of them. The phylogenetic analysis allowed to determine their homologous in other plant species and to predict their evolutionary history; and the expression profile of the FaCYP707As demonstrated that FaCYP707A3 seems to be involved in the response against salt stress in an ABA-dependent manner. Moreover, the interaction network analysis pointed out proteins involved in the ABA metabolism, heavy metal homeostasis and detoxification, and cell wall dissemble. This study characterized for the first time the CYP707A gene family in F. ananassa; this information will guide future studies in order to develop biofortified fruits and stress tolerant plants.

Autophagic Degradation of NBR1 Restricts Metastatic Outgrowth during Mammary Tumor Progression.

Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression. Though genetic ablation of autophagy strongly attenuates primary mammary tumor growth, impaired autophagy promotes spontaneous metastasis and enables the outgrowth of disseminated tumor cells into overt macro-metastases. Transcriptomic analysis reveals that autophagy deficiency elicits a subpopulation of otherwise luminal tumor cells exhibiting basal differentiation traits, which is reversed upon preventing accumulation of the autophagy cargo receptor, Neighbor to BRCA1 (NBR1). Furthermore, pharmacological and genetic induction of autophagy suppresses pro-metastatic differentiation and metastatic outgrowth. Analysis of human breast cancer data reveal that autophagy gene expression inversely correlates with pro-metastatic differentiation signatures and predicts overall and distant metastasis-free survival. Overall, these findings highlight autophagy-dependent control of NBR1 as a key determinant of metastatic progression.

High total metabolic tumor volume at baseline predicts survival independent of response to therapy.

Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) into maintenance lenalidomide or placebo. TMTV was computed on baseline positron emission tomography/computed tomography using the 41% maximum standardized uptake value method; the optimal TMTV cutoff for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301 out of 650 evaluable patients, including 192 patients classified as germinal center B-cell-like (GCB)/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3; optimal TMTV cutoff was 220 cm3. Patients with high vs low TMTV showed worse/higher Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, stage III or IV disease, >1 extranodal site, elevated lactate dehydrogenase, International Prognostic Index (IPI) 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS and OS, independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients, after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population. This trial was registered at www.clinicaltrials.gov as #NCT01122472.

Lenalidomide maintenance for diffuse large B-cell lymphoma patients responding to R-CHOP: quality of life, dosing, and safety results from the randomised controlled REMARC study.

Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on health-related quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 v3.0. The impact of TEAEs classified post hoc as subjective (patients can feel) or observable (only measurable by physicians) on dose reductions and discontinuations was assessed. Among 457 patients (lenalidomide, n = 229; placebo, n = 228), mean (standard deviation) GHS was similar between treatment arms [68·2 (20·7) Versus 72·0 (17·8)] at randomisation and remained similar during maintenance. Patients receiving lenalidomide experienced no meaningful changes in GHS, physical functioning, or fatigue. Observable TEAEs were more common (81·1% Versus 66·3%) and more likely to lead to dose reductions, than subjective TEAEs in both arms. PFS was superior in the lenalidomide arm regardless of dose reduction. Lenalidomide maintenance prolonged PFS and did not negatively impact HRQOL in patients with DLBCL despite TEAEs being more common, when compared with placebo.

Immune effector monocyte-neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer.

Metastatic behavior varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between nonmetastatic primary breast cancer and innate immune response, acting together to control metastatic progression. The primary tumor systemically recruits IFNγ-producing immune effector monocytes to the lung. IFNγ up-regulates Tmem173/STING in neutrophils and enhances their killing capacity. The immune effector monocytes and tumoricidal neutrophils target disseminated tumor cells in the lungs, preventing metastatic outgrowth. Importantly, our findings could underlie the development of immunotherapeutic target molecules that augment the function of immune effector monocytes and neutrophils.