Superparamagnetic iron oxide (SPIO) for sentinel lymph node detection in vulvar cancer.

OBJECTIVES: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer. METHODS: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer. RESULTS: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes. CONCLUSIONS: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.

Prognostic factors in young women with epithelial ovarian cancer: the Young Ovarian Cancer-Care (YOC-Care) study.

OBJECTIVE: To determine oncological outcomes and to identify prognostic factors in women aged <45 years with epithelial ovarian cancer. METHODS: A multicenter retrospective study was performed of patients treated for epithelial ovarian cancer aged <45 years between January 2010 and December 2019. RESULTS: A total of 998 patients with epithelial ovarian cancer from 55 different institutions in Spain were collected. The median age of the study population was 40.8 years (range 35.6-43.4). The grouped International Federation of Gynecology and Obstetrics (FIGO) stage distribution was 508 (50.9%) patients in initial stages (I and II) and 490 (49.1%) with advanced stages (III and IV). Three hundred and twenty-five (32.6%) patients presented with recurrent disease after a median follow-up of 33.1 months (range 16.1-66.4). The type of staging surgery (incomplete vs complete), type of initial treatment modality (primary cytoreduction vs interval surgery), and amount of residual disease were all significantly associated with overall survival. Tumor rupture was noted in 288 (27.9%) cases, but it was not associated with oncologic outcomes (p=0.11 for overall survival). In the multivariate analysis, the response based on radiological findings (HR 3.24, 95% CI 2.14 to 4.91 for partial response; HR 6.93, 95% CI 4.79 to 10.04 for progression), neoadjuvant chemotherapy (HR 1.42, 95% CI 1.04 to 1.94), and FIGO stage (HR 1.68, 95% CI 1.40 to 2.02) were identified as independent prognostic factors associated with worse oncologic outcomes (p<0.001). CONCLUSION: The partial and progression radiology-based response after chemotherapy, neoadjuvant chemotherapy, and advanced FIGO stage are independent prognostic factors associated with worse oncological outcomes in women aged <45 years with epithelial ovarian cancer.

Aortic sentinel node detection in endometrial cancer: 6 year prospective study.

OBJECTIVE: The aim of this study was to describe our final results using dual cervical and fundal indocyanine green injection for the detection of sentinel lymph nodes (SLNs) in endometrial cancer along parametrial and infundibular drainage pathways. METHODS: We conducted a prospective observational study between 26 June 2014 and 31 December 2020 enrolling 332 patients that underwent laparoscopic surgery for endometrial cancer at our hospital. In all cases, we performed SLN biopsy with dual cervical and fundal indocyanine green injection identifying pelvic and aortic SLNs. All SLNs were processed with an ultrastaging technique. A total of 172 patients also underwent total pelvic and para-aortic lymphadenectomy. RESULTS: The detection rates were as follows: 94.0% overall for SLNs; 91.3% overall for pelvic SLNs; 70.5% for bilateral SLNs; 68.1% for para-aortic SLNs, and 3.0% for isolated paraaortic SLNs. We found lymph node involvement in 56 (16.9%) cases, macrometastasis in 22, micrometastasis in 12 and isolated tumor cells in 22. Fourteen patients had isolated aortic nodal involvement, representing 25% of the positive cases. There was one false negative (SLN biopsy negative but lymphadenectomy positive). Applying the SLN algorithm, the sensitivity of the dual injection technique for SLN detection was 98.3% (95% CI 91-99.7), specificity 100% (95% CI 98.5-100), negative predictive value 99.6% (95% CI 97.8-99.9), and positive predictive value 100% (95% CI 93.8-100). Overall survival at 60 months was 91.35%, with no differences between patients with negative nodes, isolated tumor cells and treated nodal micrometastasis. CONCLUSIONS: Dual sentinel node injection is a feasible technique that achieves adequate detection rates. Additionally, this technique allows a high rate of aortic detection, identifying a non-negligible percentage of isolated aortic metastases. Aortic metastases in endometrial cancer account for as many as a quarter of the positive cases and should be considered, especially in high-risk patients.

Oncological outcomes among young women with non-epithelial ovarian cancer: the YOC-Care study (Young Ovarian Cancer - Care).

OBJECTIVE: To determine oncological outcomes and associated prognostic factors in women younger than 45 years diagnosed with non-epithelial ovarian cancer. METHODS: A retrospective, multicenter Spanish study was performed including women with non-epithelial ovarian cancer younger than 45 years between January 2010 and December 2019. All types of treatments and stages at diagnosis with at least 12 months of follow-up were collected. Women with missing data, epithelial cancers, borderline or Krukenberg tumors, and benign histology, as well as patients with previous or concomitant cancer, were excluded. RESULTS: A total of 150 patients were included in this study. The mean±SD age was 31.45±7.45 years. Histology subtypes were divided into germ cell (n=104, 69.3%), sex-cord (n=41, 27.3%), and other stromal tumors (n=5, 3.3%). Median follow-up time was 58.6 (range: 31.10-81.91) months. Nineteen (12.6%) patients presented with recurrent disease with a median time to recurrence of 19 (range: 6-76) months. Progression-free survival and overall survival did not significantly differ among histology subtypes (p=0.09 and 0.26, respectively) and International Federation of Gynecology and Obstetrics (FIGO) stage (I-II vs III-IV) with p=0.08 and p=0.67, respectively. Univariate analysis identified sex-cord histology with the lowest progression-free survival. Multivariate analysis showed that body mass index (BMI) (HR=1.01; 95% CI 1.00 to 1.01) and sex-cord histology (HR=3.6; 95% CI 1.17 to 10.9) remained important independent prognostic factors for progression-free survival. Independent prognostic factors for overall survival were BMI (HR=1.01; 95% CI 1.00 to 1.01) and residual disease (HR=7.16; 95% CI 1.39 to 36.97). CONCLUSIONS: Our study showed that BMI, residual disease, and sex-cord histology were prognostic factors associated with worse oncological outcomes in women younger than 45 years diagnosed with non-epithelial ovarian cancers. Even though the identification of prognostic factors is relevant to identify high-risk patients and guide adjuvant treatment, larger studies with international collaboration are essential to clarify oncological risk factors in this rare disease.

Effects of Iron Supplements on Heme Scavengers in Pregnancy.

In malaria endemic countries, anemia in pregnant women occurs as a result of erythrocyte destruction by Plasmodium infections and other causes including malnutrition. Iron supplementation is recommended as treatment of iron-deficiency anemia. Erythrocyte destruction results in increased release of cytotoxic free heme that is scavenged by haptoglobin (Hp), hemopexin (Hx) and heme oxygenase-1 (HO-1). Paradoxically, iron supplementation in pregnant women has been reported to enhance parasitemia and increase levels of free heme. The relationship between free heme, heme scavengers, and birth outcomes has not been investigated, especially in women who are on iron supplementation. We hypothesized that parasite-infected pregnant women on routine iron supplementation have elevated heme and altered expression of heme scavengers. A cross-sectional study was conducted to determine the association between plasma levels of free heme, HO-1, Hp, Hx, and malaria status in pregnant women who received routine iron supplementation and their birth outcomes. Heme was quantified by colorimetric assay and scavenger protein concentration by ELISA. We demonstrated that iron-supplemented women with asymptomatic parasitemia had increased free heme (mean 75.6 µM; interquartile range [IQR] 38.8-96.5) compared with nonmalaria iron-supplemented women (mean 34.9 µM; IQR 17.4-43.8, P < 0.0001). Women with preterm delivery had lower levels of Hx (mean 656.0 µg/mL; IQR 410.9-861.3) compared with women with full-term delivery (mean: 860.9 µg/mL; IQR 715.2-1055.8, P = 0.0388). Our results indicate that iron supplementation without assessment of circulating levels of free heme and heme scavengers may increase the risk for adverse pregnancy outcomes.

Elevated neuregulin-1ß levels correlate with plasma biomarkers of cerebral injury and high stroke risk in children with sickle cell anemia.

Stroke, or cerebral infarction, is one of the most serious complications of sickle cell anemia (SCA) in childhood, potentially leading to impaired development and life-long physical and cognitive disabilities. About one in ten children with SCA are at risk for developing overt stroke and an additional 25% may develop silent cerebral infarcts. This is largely due to underlying cerebral injury caused by chronic cerebral ischemia and vascular insult associated with SCA. We previously identified two elevated markers of cerebral injury, plasma brain-derived neurotropic factor (BDNF) and platelet-derived growth factor (PDGF)-AA, in children with SCA and high stroke risk. The objective of this study was to investigate whether neuregulin-1ß (NRG-1), an endogenous neuroprotective polypeptide may also be elevated in children with SCA. Neuregulin-1ß is involved in the preservation of blood brain barrier integrity and brain microvascular cell viability and is cytoprotective in conditions of heme-induced injury and ischemia. Since elevated plasma heme and ischemia are signature characteristics of SCA, we hypothesized that NRG-1 would be elevated in children with SCA, and that NRG-1 levels would also correlate with our biomarkers of cerebral injury. Plasma NRG-1, BDNF and PDGF-AA levels were measured in children with SCA and healthy Controls. Plasma NRG-1 was found to be nearly five-fold higher in those children with SCA compared to Controls. Neuregulin-1ß was also positively correlated with both BDNF and PDGF-AA concentrations, but was not associated with degree of anemia, suggesting that NRG-1 production may be an endogenous response to subclinical cerebral ischemia in SCA warranting further exploration.

Relación entre determinantes sociales de salud y perfil de funcionamiento de personas con discapacidad del municipio Los Patios, Norte de Santander, Colombia / Relationship between social determinants of health and functioning profile of people with disabilities from Los Patios Municipality, Norte de Santander, Colombia

RESUMEN Objetivo Analizar la relación de los determinantes sociales en salud con el perfil de funcionamiento de personas con discapacidad del municipio Los Patios, Norte de Santander. Método A una muestra de 246 personas con algún tipo de discapacidad del municipio Los Patios, Norte de Santander, bajo selección no probabilística intencionada, se administraron los instrumentos denominados Registro para la Localización y Caracterización de Personas con Discapacidad (RLPCD) y el del perfil de funcionamiento según la Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud (CIF), para identificar los determinantes sociales de salud y el perfil de funcionamiento, y determinar su relación. Resultados La muestra se caracterizó por un mayor porcentaje de hombres con discapacidad (60,2%), en relación con las mujeres (39,8%), residentes en estratos socioeconómicos 1,2 y 3 y grupos etarios entre 5 y 93 años, con un alto porcentaje que no recibe algún tipo de ingreso (79,2%). Las principales discapacidades que presentaron fueron de movilidad y su grado de funcionamiento se ubicó entre no deficiencia y deficiencia moderada, con una relación de dependencia con los determinantes sociales de salud. Conclusiones El estudio muestra evidente relación entre los determinantes sociales y el perfil de funcionamiento de personas con discapacidad. Género, nivel de escolaridad, ingresos y estrato socioeconómico son elementos que determinan el grado de funcionalidad de individuos con discapacidad. Estos factores se deben considerar cuando se desarrollan políticas públicas orientadas al beneficio de este tipo de población; Tenerlos en cuenta podría garantizar el éxito en la aplicación de las políticas diseñadas.(AU)

ABSTRACT Objective To analyze the relationship between social factors in health with the functioning profile of people with disabilities in the municipality of Los Patios, Norte de Santander. Method A sample of 246 people with a type of disability in the municipality Los Patios, Norte de Santander, under intentional non-probabilistic selection, were studied using the Registry for the Location and Characterization of Persons with Disabilities (RLPCD) and the functioning profile of people with disabilities (CIF) to identify the social determinants of health and the functioning profile, and determine their relationship. Results The sample was characterized by a higher percentage of men with disabilities (60.2%), in relation to women (39.8%), members in socioeconomic strata 1, 2 and 3 and age groups between 5 and 93 years old, with a high percentage that does not receive any type of income (79.2%). The main disabilities identified were mobility and the degree of functioning located between no deficiency and moderate deficiency with a relationship of dependence with the social determinants of health. Conclusions The study shows an evident relationship between the social determinants and the functioning profile of people with disabilities. Gender, level of education, income and socioeconomic status are elements that determine the degree of functionality of people with disabilities. It is fundamental, in the development of public policies aimed at the well-being of this type of population, that these factors are considered to ensure success in the implementation of appropriate policies.(AU)

Modelling heme-mediated brain injury associated with cerebral malaria in human brain cortical organoids.

Human cerebral malaria (HCM), a severe encephalopathy associated with Plasmodium falciparum infection, has a 20-30% mortality rate and predominantly affects African children. The mechanisms mediating HCM-associated brain injury are difficult to study in human subjects, highlighting the urgent need for non-invasive ex vivo human models. HCM elevates the systemic levels of free heme, which damages the blood-brain barrier and neurons in distinct regions of the brain. We determined the effects of heme on induced pluripotent stem cells (iPSCs) and a three-dimensional cortical organoid system and assessed apoptosis and differentiation. We evaluated biomarkers associated with heme-induced brain injury, including a pro-inflammatory chemokine, CXCL-10, and its receptor, CXCR3, brain-derived neurotrophic factor (BDNF) and a receptor tyrosine-protein kinase, ERBB4, in the organoids. We then tested the neuroprotective effect of neuregulin-1 (NRG-1) against heme treatment in organoids. Neural stem and mature cells differentially expressed CXCL-10, CXCR3, BDNF and ERBB4 in the developing organoids and in response to heme-induced neuronal injury. The organoids underwent apoptosis and structural changes that were attenuated by NRG-1. Thus, cortical organoids can be used to model heme-induced cortical brain injury associated with HCM pathogenesis as well as for testing agents that reduce brain injury and neurological sequelae.

Efficacy of a Fibrin Sealant (Tissucol Duo) for the Preventionof Lymphocele after Laparoscopic Pelvic Lymphadenectomy:A Randomized Controlled Trial.

STUDY OBJECTIVE: To assess the efficacy of Tissucol Duo (Baxter AG, Vienna, Austria) fibrin sealant in decreasing the incidence of lymphocele (LC) after pelvic laparoscopic lymph node dissection using harmonic shears. DESIGN: Randomized controlled trial (Canadian Task Force classification level I). SETTING: Tertiary referral and educational center. PATIENTS: Seventy-four patients randomized to the use of sealant per hemipelvis. INTERVENTION: Fibrin sealant. MEASUREMENTS AND MAIN RESULTS: After bilateral pelvic lymphadenectomy a fibrin sealant was used in 1 hemipelvis but not the other, applied in 41 patients (55.4%) to the left and 33 patients (44.6%) to the right hemipelvis. The primary outcome was the incidence of LC after surgery in symptomatic and asymptomatic patients. Imaging (ultrasound, computed tomography, and magnetic resonance) was performed to detect LC at 3, 6, and 12 months after surgery. Overall, 26 patients (35.1%) developed LC, and 4 were symptomatic (5.4%). Allowing patients to serve as their own treatment group and control, the hemipelvis treated with Tissucol Duo corresponding to the treatment group and that not treated to the control group, LCs were found in 17 (23%) and 14 (19%) cases, respectively, but the difference was not significant. The mean initial LC maximum diameter was 27.1 mm (standard deviaiotn, 35.2), and LCs tended to decrease in size during the first year to a mean of 8.7 mm. CONCLUSION: Application of Tissucol Duo fibrin sealant after laparoscopic pelvic lymphadenectomy using ultrasonic shears does not decrease the occurrence of symptomatic or asymptomatic LC.

Neuregulin-1 attenuates experimental cerebral malaria (ECM) pathogenesis by regulating ErbB4/AKT/STAT3 signaling.

BACKGROUND: Human cerebral malaria (HCM) is a severe form of malaria characterized by sequestration of infected erythrocytes (IRBCs) in brain microvessels, increased levels of circulating free heme and pro-inflammatory cytokines and chemokines, brain swelling, vascular dysfunction, coma, and increased mortality. Neuregulin-1ß (NRG-1) encoded by the gene NRG1, is a member of a family of polypeptide growth factors required for normal development of the nervous system and the heart. Utilizing an experimental cerebral malaria (ECM) model (Plasmodium berghei ANKA in C57BL/6), we reported that NRG-1 played a cytoprotective role in ECM and that circulating levels were inversely correlated with ECM severity. Intravenous infusion of NRG-1 reduced ECM mortality in mice by promoting a robust anti-inflammatory response coupled with reduction in accumulation of IRBCs in microvessels and reduced tissue damage. METHODS: In the current study, we examined how NRG-1 treatment attenuates pathogenesis and mortality associated with ECM. We examined whether NRG-1 protects against CXCL10- and heme-induced apoptosis using human brain microvascular endothelial (hCMEC/D3) cells and M059K neuroglial cells. hCMEC/D3 cells grown in a monolayer and a co-culture system with 30 µM heme and NRG-1 (100 ng/ml) were used to examine the role of NRG-1 on blood brain barrier (BBB) integrity. Using the in vivo ECM model, we examined whether the reduction of mortality was associated with the activation of ErbB4 and AKT and inactivation of STAT3 signaling pathways. For data analysis, unpaired t test or one-way ANOVA with Dunnett's or Bonferroni's post test was applied. RESULTS: We determined that NRG-1 protects against cell death/apoptosis of human brain microvascular endothelial cells and neroglial cells, the two major components of BBB. NRG-1 treatment improved heme-induced disruption of the in vitro BBB model consisting of hCMEC/D3 and human M059K cells. In the ECM murine model, NRG-1 treatment stimulated ErbB4 phosphorylation (pErbB4) followed by activation of AKT and inactivation of STAT3, which attenuated ECM mortality. CONCLUSIONS: Our results indicate a potential pathway by which NRG-1 treatment maintains BBB integrity in vitro, attenuates ECM-induced tissue injury, and reduces mortality. Furthermore, we postulate that augmenting NRG-1 during ECM therapy may be an effective adjunctive therapy to reduce CNS tissue injury and potentially increase the effectiveness of current anti-malaria therapy against human cerebral malaria (HCM).

Estrategias terapéuticas para aumentar la eficacia de la tos en pacientes con enfermedades neuromusculares / Therapeutic strategies to increase the effectiveness of cough

Cough is a natural reflex that protects respiratory airways against infections or mucus retention. Cough maintains an adequate cleaning of the airways and is a mainstay of respiratory therapy. It can be triggered voluntarily by the patient or by a specific cough device. Peak cough flow (PCF) is used to assess the effectiveness of the cough. When this value is below 160 L/min, cough is considered inefficient and becomes a risk factor for respiratory problems. Patients with weak cough, especially those with neuromuscular disease, have in common a low tidal volume and a decreased maximum insufflation capacity. Both factors directly affect the inspiratory phase previous to cough, which is considered vital to obtain the optimum flow for a productive cough. Different therapeutic measures may help to increase cough efficiency among patients with cough weakness. These interventions may be performed using manual techniques or by mechanical devices. The aim of this review is to analyze the different techniques available for cough assistance, set a hierarchy of use and establish a scientific basis for their application in clinical practice.

Absceso cerebral en niños: una complicación de otomastoiditis crónica de diagnóstico tardío / Brain abscess in children: a complication of late diagnosis chronic mastoiditis

Reportamos el caso de una paciente de 7 años de edad que presentó otitis media aguda complicada con otomastoiditis crónica quien fue operada de una timpanomastoidectomía a los dos meses y medio de enfermedad, a los tres meses presentó fiebre, signos de hipertensión endocraneana y paresia del miembro superior izquierdo. La tomografía espiral multicorte mostró absceso en el lóbulo temporal ipsilateral. Recibió tratamiento antibiótico de amplia cobertura y fue sometida a resección quirúrgica del absceso. Seis semanas después de la intervención quirúrgica salió de alta con monoparesia del brazo izquierdo con desempeño independiente.

We report a case of a seven year old patient who had acute media otitis complicated with chronic otomastoiditis, who was operated of timpanomastoidectomy after two months and a half of illness, at three months she had fever, endocraneal hypertension signs and paresia of the left upper limb. The multislice spiral tomography showed the presence of an abscess on the ipsilateral temporal lobe. She received extended-spectrum antibiotic therapy and surgical excision of the abscess. Six weeks after the surgery she was discharged from the hospital with left upper limb monoparesia with independent performance.

Efectos de la reforma de la seguridad social en salud en Colombia sobre la equidad en el acceso y la utilización de servicios de salud / Effects of the social security reform in Colombia on equity to access and use of health services

Para evaluar los efectos del nuevo sistema de salud sobre la equidad en el acceso y la utilización de los servicios de salud, se compararon dos cortes transversales de la población antes de la Ley 100 de 1993 que creó el Sistema General de Seguridad Social en Salud (SGSSS) y después de la misma. Se evaluaron los cambios en la distribución de un indicador de equidad en el acceso a los servicios de salud: afiliación al SGSSS; adicionalmente, se compararon dos grupos de población en el corte de 1997, afiliados y no afiliados al sistema de SGSSS, con el fin de evaluar los cambios en la distribución de dos indicadores de equidad en la utilización de servicios: hospitalización y uso de servicios de salud en general. Los resultados obtenidos, revelan que entre 1993 y 1997, la cobertura del SGSSS aumentó del 23/100 al 57/100. El aumento en la cobertura fué más dramático entre los segmentos más pobres de la población: en los hogares del primer decil de ingresos la cobertura aumentó del 3.1/100 al 43.7/100 y el índice de concentración en la distribución de la afiliación al SGSSS se redujo a la mitad: del 0.34 a 0.17. En cambio, los indicadores de concentración correspondientes a la utilización de servicios variaron muy poco inclusive luego del ajuste hecho por edad, género y necesidades. Estos resultados sugieren un impacto positivo del SGSSS sobre las inequidades en el acceso, pero los efectos sobre las inequidades en la utilización de los servicios de salud no son claros.

Aneurisma de ventrículo esquerdo associado à comunicaçäo interventricular pós-infarto / Aneurysm of left ventricle associated with post-infarction interventricular communication

Dois homens sexagenários apresentaram aneurisma do ventrículo esquerdo associado a comunicaçäo interventricular (CIV), na evoluçäo de infarto do miocárdio anterior extenso e ínfero-anterior. Os pacientes foram submetidos com sucesso a aneurismectomia ventricular esquerda, a revascularizaçäo do miocárdio e a fechamento da CIV