Consenso SOCHOG/SOCHUMB: utilizar en Chile la curva estándar OMS ultrasonográfica de crecimiento fetal / SOCHOG/SOCHUMB consensus: OMS fetal ultrasound curve is the standard curve for ultrasound growth assessment to use in Chile

La Sociedad Chilena de Obstetricia y Ginecología (SOCHOG) y la Sociedad Chilena de Ultrasonido en Medicina y Biología (SOCHUMB) convocaron a un comité de expertos en el tema de ultrasonido y crecimiento fetal con el fin de proponer utilizar la curva fetal que mejor se adapte a la población chilena. Luego de la discusión, al no contar con curvas chilenas de crecimiento fetal, se concluye proponer que la curva estándar de la Organización Mundial de la Salud (OMS) sería la indicada dada la calidad de su metodología y por ser multicéntrica.

The Chilean Society of Obstetrics and Gynecology (SOCHOG) and the Chilean Society of Ultrasound in Medicine and Biology (SOCHUMB) have convened a committee of experts on the subject of ultrasound and fetal growth in order to propose using the fetal curve that best adapts to the Chilean population. After the discussion, since there are no Chilean fetal growth curves, it is concluded that the World Health Organization (WHO) standard curve would be the one to use given the quality of its methodology and the fact that it is multicentric.

Practice-Changing Use of the 21-Gene Test for the Management of Patients With Early-Stage Breast Cancer in Latin America.

PURPOSE: We present a physician survey of the impact of 21-gene Breast Recurrence Score test results on treatment decisions in clinical practice in Latin America. METHODS: This prospective survey enrolled consecutive patients at 14 sites in Argentina, Colombia, Mexico, and Peru who had routine 21-gene testing. Physician surveys captured patient and tumor characteristics and treatment decisions before and after 21-gene test results. The survey spanned the period before and after Trial Assigning Individualized Options for Treatment (TAILORx) results reported (June 2018). Overall net percent change in adjuvant chemotherapy recommendations was estimated, and asymptotic 95% CIs with continuity correction were calculated. The proportion with a change between pretest treatment recommendation and actual treatment received was calculated overall and by Recurrence Score groups per TAILORx. RESULTS: Between March 2015 and December 2019, the survey was completed for 647 patients; 20% were node-positive. The mean patient age was 54 years (24-85 years); 55% were postmenopausal; 17%, 63%, and 20% had grade 1, 2, and 3 tumors, respectively; and 30% had tumors > 2 cm. Recurrence Score (RS) results were as follows: 20% RS 0-10, 56% RS 11-25, and 24% RS 26-100. Overall, chemotherapy recommendations fell by a relative proportion of 39% (95% CI, 33.4 to 44.3) after 21-gene testing (33% decrease in node-negative and 55% decrease in node-positive). Among node-negative patients, the relative decrease in chemotherapy recommendations was 28% (95% CI, 18.9 to 39.5) before TAILORx and 36% (95% CI, 28.4 to 43.7) after. CONCLUSION: To our knowledge, this large survey of 21-gene test practice patterns was the first conducted in Latin America and showed the relevance of 21-gene testing in low- and medium-resource countries to minimize chemotherapy overuse and underuse in breast cancer. The results showed substantial reductions in chemotherapy use overall-especially after TAILORx reported-indicating the practice-changing potential of that study.

In silico Accuracy and Energy Efficiency of Two Steering Paradigms in Directional Deep Brain Stimulation.

Background: In Deep Brain Stimulation (DBS), stimulation field steering is used to achieve stimulation spatial specificity, which is critical to obtain clinical benefits and avoid side effects. Multiple Independent Current Control (MICC) and Interleaving/Multi Stim Set (Interleaving/MSS) are two stimulation field steering paradigms in commercially available DBS systems. This work investigates the stimulation field steering accuracy and energy efficiency of these two paradigms in directional DBS. Methods: Volumes of Tissue Activated (VTAs) were generated in silico using pulse widths of 60 µs and five pulse amplitude fractionalizations intended to steer the VTAs radially in 12° steps. For each fractionalization, VTAs were generated with nine pre-defined target radii. Stimulation field steering accuracy was assessed based on the VTAs rotation angle. Energy efficiency was inferred from current draw from battery values, which were calculated based on the pulse amplitudes needed to generate and steer the VTAs, as well as electrode impedance measurements of clinically implanted directional leads. Results: For radial steering, MICC needed a single VTA. In contrast, Interleaving/MSS required the generation of two VTAs, whose union and intersection created an Interleaving/MSS VTA and an Intersection VTA, respectively. MICC VTAs were 6.8 (-3.2-11.8)% larger than Interleaving/MSS VTAs. The Intersection VTAs accounted for 26.2 (16.0-32.8)% of Interleaving/MSS VTAs and were exposed to a higher stimulation frequency. For all VTA radius-fractionalization combinations, steering accuracy was 7.0 (4.5-10.5)° for MICC and 24.0 (9.0-25.3)° for Interleaving/MSS. Pulse amplitudes were 16.1 (9.2-28.6)% lower for MICC than for Interleaving/MSS, leading to a 45.9 (18.8-72.6)% lower current draw from battery for MICC. Conclusions: The results of this work show that in silico, MICC achieves a significantly better stimulation field steering accuracy and has a significantly higher energy efficiency than Interleaving/MSS. Although direct evidence still needs to be generated to translate the results of this work to clinical practice, clinical outcomes may profit from the better stimulation field steering accuracy of MICC and longevity of DBS systems may profit from its higher energy efficiency.

Mercury Mining in Mexico: I. Community Engagement to Improve Health Outcomes from Artisanal Mining.

BACKGROUND: Mercury is an element that cannot be destroyed and is a global threat to human and environmental health. In Latin America and the Caribbean, artisanal and small-scale gold mining represents the main source of mercury emissions, releases, and consumption. However, another source of concern is the primary production of mercury. In the case of Mexico, in the past 2 years the informal production of mercury mining has increased 10-fold. Considering this scenario, an intervention program was initiated to reduce health risks in the mining communities. The program's final goal is to introduce different alternatives in line to stop the mining of mercury, but introducing at the same time, a community-based development program. OBJECTIVE: The aim of this study was to present results from a preliminary study in the community of Plazuela, located in the municipality of Peñamiller in the State of Queretaro, Mexico. METHODS: Total mercury was measured in urine and environmental samples using atomic absorption spectrometry by cold vapor technique. Urine samples were collected from children aged 6-14 years and who had lived in the selected area from birth. Urine samples were also collected from miners who were currently working in the mine. To confirm the presence of mercury in the community, mining waste, water, soil, and sediment samples were collected from those high-risk areas identified by members of the community. FINDINGS: Children, women, and miners were heavily exposed to mercury (urine samples); and in agreement, we registered high concentrations of mercury in soils and sediments. CONCLUSION: Considering these results and taking into account that the risk perception toward mercury toxicity is very low in the community (mining is the only economic activity), an integral intervention program has started.

Extended transvaginal sonography in deep infiltrating endometriosis: use of bowel preparation and an acoustic window with intravaginal gel: preliminary results.

OBJECTIVES: The purpose of this study was to assess the diagnostic performance of extended transvaginal sonography for diagnosing deep infiltrating endometriosis. METHODS: A prospective study was conducted comprising 51 women (mean age, 32.9 years; range, 23-43 years) with suspected deep infiltrating endometriosis based on clinical symptoms. All women underwent extended transvaginal sonography, which included assessment of 2 pelvic compartments (anterior compartment: bladder and distal ureters; and posterior compartment: posterior vaginal fornix, retrocervical area, pouch of Douglas, and rectosigmoid). The sliding sign for detecting pouch of Douglas obliteration was also assessed. All patients received bowel preparation before sonographic examinations. A single examiner performed all examinations. All women underwent laparoscopic surgery, and histologic confirmation of endometriosis was done. The sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were calculated. RESULTS: Some women had more than 1 lesion, giving a total of 55 histologically confirmed lesions (rectosigmoid, n = 13; vagina, n = 5; retrocervical, n = 32; bladder, n = 5). The sensitivity, specificity, and LR+ for rectosigmoid involvement were 100%, 93%, and 14.0, respectively. The sensitivity, specificity, LR+, and LR- for vaginal involvement were 60%, 98%, 30.0, and 0.41. The sensitivity, specificity, LR+, and LR- for retrocervical involvement were 84%, 96%, 19.4, and 0.16. The sensitivity, specificity, and LR- for bladder involvement were 20%, 100%, and 0.80. The sensitivity, specificity, LR+, and LR- of the sliding sign for diagnosing pouch of Douglas obliteration were 89%, 92%, 10.7, and 0.12. CONCLUSIONS: Except for bladder involvement, extended transvaginal sonography has good diagnostic performance for deep infiltrating endometriosis.

Plica sinovial dolorosa asociada a condromalacia radiocapitelar: reporte de caso / Synovial wris impingement with concomitant radial-capitelar chondromalacia: case report

Las plicas sinoviales de la articulación radiocapitelar pueden causar crepitación dolorosa de la articulación del codo y se deben diferenciar de otras causas de crepitación dolorosa del codo como los cuerpos libres intraarticulares, la inestabilidad o la luxación medial de la cabeza del tríceps sobre el epicóndilo medial. El dolor sobre la cara lateral del codo, acompañado de sensación de resalto en flexión y pronación, es un hallazgo común en los pacientes con dicha patología. El tratamiento con cirugía artroscópica del codo generalmente confirma la presencia de la plica sinovial asociada a un área adyacente de sinovitis y una lesión del cartílago de la cabeza radial y el capitelo. Se presenta el caso de una paciente joven con una plica sinovial dolorosa con una condromalacia radiocapitelar asociada.

Breast cancer classification according to immunohistochemistry markers: subtypes and association with clinicopathologic variables in a peruvian hospital database.

BACKGROUND: Molecular classification is an excellent prognostic and predictive method in breast cancer (BC). In this study. we evaluated differences in clinicopathologic features and overall survival (OS) in four BC molecular subtypes: luminal A, luminal B, basal cell-like, and HER2/neu. PATIENTS AND METHODS: Immunohistochemical evaluation of estrogen receptor (ER), progesterone receptor (PgR), and HER2 was performed using a Peruvian hospital database of 1198 BC patients who were diagnosed between 2000 and 2002. Overall survival was calculated. RESULTS: Out of 1198 patients with invasive BC, 49.3% were luminal A; 13.2%, luminal B; 21.3%, basal-like; and 16.2%, HER2. The mean of age at diagnosis was 51.5 years for luminal A; 49.6 for luminal B; 49.5 for basal-like; and 49.4 for HER2. The HER2 subtype showed 63.7% positive lymph nodes, 42.3% stage III and 9.7% stage IV cases. Basal subtypes showed the highest prevalence of a poorly differentiated phenotype (70.3%). Average follow-up was 60 months. Five-year OS was significantly different between all 4 groups (P < .0001); luminal A had the highest OS, followed by luminal B, basal-like; and HER2. Results are compared with other population studies. CONCLUSION: This study shows significant differences between the distribution of molecular subtypes and clinicopathologic features. Immunohistochemistry is useful in the clinical management of BC patients.

Gynecologic imaging reporting and data system: a new proposal for classifying adnexal masses on the basis of sonographic findings.

OBJECTIVE: The purpose of this study was to describe a new reporting system called the Gynecologic Imaging Reporting and Data System (GI-RADS) for reporting findings in adnexal masses based on transvaginal sonography. METHODS: A total of 171 women (mean age, 39 years; range, 16-77 years) suspected of having an adnexal mass were evaluated by transvaginal sonography before treatment. Pattern recognition analysis and color Doppler blood flow location were used for determining the presumptive diagnosis. Then the GI-RADS was used, with the following classifications: GI-RADS 1, definitively benign; GI-RADS 2, very probably benign; GI-RADS 3, probably benign; GI-RADS 4, probably malignant; and GI-RADS 5, very probably malignant. Patients with GI-RADS 1 and 2 tumors were treated expectantly. All GI-RADS 3, 4, and 5 tumors were removed surgically, and a definitive histologic diagnosis was obtained. The GI-RADS classification was compared with final histologic diagnosis. RESULTS: A total of 187 masses were evaluated. The prevalence rate for malignant tumors was 13.4%. Overall GI-RADS classification rates were as follows: GI-RADS 1, 4 cases (2.1%); GI-RADS 2, 52 cases (27.8%); GI-RADS 3, 90 cases (48.1%); GI-RADS 4, 13 cases (7%); and GI-RADS 5, 28 cases (15%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 92%, 97%, 85%, 99%, and 96%, respectively. CONCLUSIONS: Our proposed reporting system showed good diagnostic performance. It is simple and could facilitate communication between sonographers/sonologists and clinicians.

Compromiso del complejo areola pezón en mastectomía por cáncer de mama / Commitment nipple areola complex in mastectomy for breast cancer

Background: was to investigate the predictors of injection of the nipple areola complex in breast cancer patients to define the indications for mastectomy with immediate reconstruction preserving the skin and nipple areola complex, at Instituto Nacional de Enfermedades Neoplásicas. Methods: randomly reviewed 100 clinical records of patients diagnosed with breast cancer undergoing mastectomy, including patients with diagnosis in Instituto Nacional de Enfermedades Neoplasicas, excluding patients treated with surgery in another institution or tratmiento neoadjuvant chemotherapy or radiotherapy. Results: only 76 patients met the inclusion Criterior. The average age 47.32, the most common location in the breast was tunor the outer surface quadrants, the average distance from the nipple is 33,25 mm. .The average size of tumors is of 30.66 mm (range, 2 to 70 mm). The most common histological type is ductal cancer, 52 breast (68.4%). 25% of this undertaking paceintes nipple areola complex. Multicentricity correlate with the state of the nipple. Conclusions: We found a significant association between nipple areola commitment multicentricity.

The change of the scFv into the Fab format improves the stability and in vivo toxin neutralization capacity of recombinant antibodies.

The antigen-binding fragment (Fab) has been considered a more functionally stable version of recombinant antibodies than single chain antibody fragments (scFvs), however this intuitive consideration has not been sufficiently proven in vivo. This communication shows that three out of four specific scFvs against a scorpion toxin, with different affinities and stabilities, become neutralizing in vivo when expressed as Fabs, despite the fact that they are not neutralizing in the scFv format. A scFv fragment previously obtained from a neutralizing mouse antibody (BCF2) was used to produce three derived scFvs by directed evolution. Only one of them was neutralizing, however when expressed as Fab, all of them became neutralizing fragments in vivo. The initial scFvBCF2 (earlier used for directed evolution) was not neutralizing in the scFv format. After expressing it as Fab did not become a neutralizing fragment, but did reduce the intoxication symptoms of experimental mice. The stability of the four Fabs derived from their respective scFvs was improved when tested in the presence of guanidinium chloride. The in vitro stability of the Fab format has been shown earlier, but the physiological consequences of this stability are shown in this communication. The present results indicate that improved functional stability conferred by the Fab format can replace additional maturation steps, when the affinity and stability are close to the minimum necessary to be neutralizing.

Design and validation of a synthetic VH repertoire with tailored diversity for protein recognition.

Previous studies have indicated differences in the specificity-determining residues (SDRs) of antibodies that recognize haptens, peptides, or proteins. Here, we designed a V(H) repertoire based on the human scaffold 3-23/J(H)4 and diversification of high and medium-usage SDRs of anti-protein and anti-peptide antibodies. The repertoire was synthesized by overlapping polymerase chain reaction (PCR) and combined with the V(L) chain of the anti-hen egg-white lysozyme (HEL) antibody D1.3. The resulting chimeric single-chain Fv fragments (scFvs) phage-displayed library was panned in HEL-coated immunotubes. After two rounds of selection under non-stringent conditions, that is, trypsinization after 2 h of incubation at room temperature, 63 of 167 clones analyzed (38%) were found to express scFvs specific to HEL. Twenty clones were characterized by DNA sequencing resulting in 10 unique scFvs. Interestingly, the panel of unique scFvs was highly diverse, with V(H) sequences differing in 16 of the 17 positions variegated in the repertoire. Thus, diverse chemico-physical and structural solutions were selected from the library, even when the V(H) repertoire was constrained by the V(L) chain of D1.3 to yield binders against a definite region of HEL surface. The more often selected scFvs, namely H6-1 and B7-1, which differed in eight SDRs, showed levels of expression in E. coli TG1 strain, 6 and 10 times higher than the parental D1.3 Fv fragment, respectively. Dissociation constants (K(Ds)) measured in the BIAcore were 11 and 6.6 nM for H6-1 and B7-1, respectively. These values compared well to the K(D) of 4.7 nM measured for D1.3, indicating that the V(H) repertoire here designed is a valuable source of diverse, well-expressed and high affinity V(H) domains.

A strategy for the generation of specific human antibodies by directed evolution and phage display. An example of a single-chain antibody fragment that neutralizes a major component of scorpion venom.

This study describes the construction of a library of single-chain antibody fragments (scFvs) from a single human donor by individual amplification of all heavy and light variable domains (1.1 x 10(8) recombinants). The library was panned using the phage display technique, which allowed selection of specific scFvs (3F and C1) capable of recognizing Cn2, the major toxic component of Centruroides noxius scorpion venom. The scFv 3F was matured in vitro by three cycles of directed evolution. The use of stringent conditions in the third cycle allowed the selection of several improved clones. The best scFv obtained (6009F) was improved in terms of its affinity by 446-fold, from 183 nm (3F) to 410 pm. This scFv 6009F was able to neutralize 2 LD(50) of Cn2 toxin when a 1 : 10 molar ratio of toxin-to-antibody fragment was used. It was also able to neutralize 2 LD(50) of the whole venom. These results pave the way for the future generation of recombinant human antivenoms.

Proceso para el desarrollo de una vacuna contra la fase hepática de Plasmodium vivax / Process to development a vaccine against to hepatic phase of Plasmodium vivax

Introducción: Anualmente se producen en el mundo entre 80 y 100 millones de casos de malaria ocasionada por Plasmodium vivax, segunda especie de Plasmodium en importancia a nivel mundial y primera en el continente americano. Ante la falla de los métodos clásicos de control de la malaria, derivada de la creciente resistencia de los mosquitos a los insecticidas y de los parásitos a los medicamentos disponibles, se ha trabajado intensamente en la búsqueda de vacunas que puedan prevenir completamente la infección o limitar los efectos patológicos de la enfermedad. Objetivos: Este trabajo describe el proceso de desarrollo de una vacuna experimental dirigida contra las formas pre-eritrocíticas del parásito, para lo cual se ha seleccionado la proteína circumesporozoito (CS) que se expresa de forma abundante en la superficie del parásito y que se halla comprometida en el proceso de invasión hepática. Metodología: El proceso consistió en una exhaustiva caracterización inmunológica de la proteína, mediante péptidos sintéticos de diferente longitud, seguida de pruebas de toxicidad e inmunogenicidad en animales con los tres péptidos largos que cubren las regiones N, R y C de la CS. Como etapa inicial de la prueba en humanos, se hizo un ensayo clínico fase I que probó la seguridad e inmunogenicidad, de cada uno de los péptidos formulados en el adyuvante Montanide ISA-720. El ensayo fue al azar, doble ciego y comprometió a 23 voluntarios sanos, hombres y mujeres entre 18 y 33 años de edad, sin historia de malaria. Conclusiones: La vacuna fue muy bien tolerada y demostró buena seguridad e inmunogenicidad en los ensayos preclínicos así como en todos los voluntarios, facilitando el avance a ulteriores fases de investigaciónclinica

Quimioterapia de inducción y tratamiento de conservación en cáncer de mama estadío clínico II / Induction chemotherapy and conservation treatment in cancer of he/she suckles clinical stage II

Objetivo: Se ha comparado el tratamiento estándar de conservación en cáncer de mama estadío clínico II (Tumorectomía + Disección Radical de Axila y Radioterapia a la Mama), con quimioterapia de inducción y tratamiento estándar, y un tercer tratamiento de quimioterapia de inducción + tumorectomía y disección radical de axila sin radioterapia a la mama. Este es un trabajo piloto de investigación clínica, prospectivo, randomizado eil 3 grupos de intervención, descriptivo y analítico. Materiales y Métodos: ingresaron al presente estudio 112 pacientes que fueron randomizados en los tres brazos con 41, 34, 37 pacientes respectivamente, la evaluación estadística demostró de que los tres brazos eran comparables. Se investigó respuesta clínica, radiológica y patológica a la quimioterapia neoadyuvante, así se comparó recurrencia local, sobrevida libre de enfermedad y sobrevida total con un seguimiento mínimo de 30 meses y máxima de 65 meses. Resultados y Conclusiones: La respuesta clínica a la quimioterapia fué: parcial 49.2 por ciento, completa 15,4 por ciento y en 35.2 por ciento no se obtuvo respuesta. La respuesta radiológica fue: parcial 45.6 por ciento y completa 19.5 por ciento. Desde el punto de vista anatomopatológico, en el 5.6 por ciento no se encontró neoplasia residual en la mama y en el 2.8 por ciento solo había carcinoma intraductal. La recurrencia local fue menor en las pacientes que tuvieron tratamiento de conservación estándar 7.3 por ciento si se compara con los brazos que tuvieron quimioterapia neodyuvante. Las pacientes que no tuvieron radioterapia a la mama recurrieron en el 48.3 por ciento de los casos. Tuvieron mayor recurrencia las pacientes en las que se encontró bordes infiltrados de tumor y metástasis axilar masiva (10 a más ganglios tomados). La sobrevida total y la sobrevida libre de enfermedad es similar en los tres brazos estudiados mediante curvas de Kaplan-Meyer.