Optional screening strategies for cervical cancer using standalone tests and their combinations among low- and medium-income populations in Latin America and Eastern Europe

The performance of cervical cancer (CC) screening can be improved by combining Pap smear with human papillomavirus (HPV) testing or visual methods, addressing local demographic, clinical and economic characteristics.The NIS Cohort study was supported by the INCO-CopernicusProgramoftheEuropeanCommission(Contract No. ERB IC15-CT98 – 0321), and the LAMSstudy by the European Commission, INCO-DEV Program(Contract# ICA4-CT-2001 – 10013). We express specialthanks to the former Digene Corp. for providing theHybrid Capture analyser, samplers and the test kits at ourdisposal. We express our thanks to all women who partici-pated in these two cohort studies. Finally, all the membersof the NIS and LAMS Study research groups are acknowl-edged for their invaluable contribution to these studies

Manejo de la neoplasia ntraepitelial cervical

El 80 % de las mujeres sexualmente activas se infectan por HPV a lo largo de su vida, siendo más frecuente en etapas tempranas. La mayoría de las veces son asintomáticas y más del 90 % se eliminan por el sistema inmunitario del huésped en los primeros dos años; sin embargo, el 10 % persisten y eventualmente culminan en lesiones malignas. Más del 90 % de los cánceres de cuello uterino en el mundo están causados por HPV. El 55 % se asocian a HPV genotipo 16, el 15 % al HPV genotipo 18; seguidos por los genotipos 31, 33, 35, 45, 52 y 58 que engloban el 18 %. Para el manejo adecuado de las lesiones intraepiteliales (LIE) cervicales, es de suma importancia tener en claro la manera correcta y actualizada de cada método, las guías vigentes, y las utilidades de cada uno. El antiguo trípode diagnóstico clásico que consta de citología, colposcopía y biopsia está perdiendo vigencia, ya que a los métodos diagnósticos actualmente se incorporan las técnicas de inmunohistoquímica y biología molecular. El objetivo principal del tratamiento de las lesiones intraepiteliales del cuello uterino es evitar el cáncer, siendo las lesiones de alto grado las de principal relevancia clínica. El cáncer de cuello uterino continúa siendo una causa relevante de muerte en Argentina y Latinoamérica, siendo de vital importancia que los ginecólogos manejen adecuadamente los algoritmos diagnósticos y terapéuticos de las lesiones intraepiteliales del cuello uterino, además de la adecuada implementación de programas nacionales de salud pública.Facultad de Ciencias Médica

Up-regulation of 14-3-3sigma (Stratifin) is associated with high-grade CIN and high-risk human papillomavirus (HPV) at baseline but does not predict outcomes of HR-HPV infections or incident CIN in the LAMS study

To assess whether the potentially high-risk (HR) human papillomavirus (HPV)-related up-regulation of 14-3-3sigma (stratifin) has implications in the outcome of HPV infections or cervical intraepithelial neoplasia (CIN) lesions, cervical biopsy specimens from 225 women in the Latin American Screening Study were analyzed for 14-3-3sigma expression using immunohistochemical analysis. We assessed its associations with CIN grade and HR HPV at baseline and value in predicting outcomes of HR-HPV infections and the development of incident CIN 1+ and CIN 2+. Expression of 14-3-3sigma increased in parallel with the lesion grade. Up-regulation was also significantly related to HR-HPV detection (P = .004; odds ratio, 2.71; 95% confidence interval, 1.37-5.35) and showed a linear relationship to HR-HPV loads (P = .003). 14-3-3sigma expression was of no value in predicting the outcomes (incident, persistent, clearance) of HR-HPV infections or incident CIN 1+ and CIN 2+. 14-3-3sigma is not inactivated in cervical carcinoma and CIN but is up-regulated on transition from CIN 2 to CIN 3. Its normal functions in controlling G(1)/S and G(2)/M checkpoints are being bypassed by HR HPV.LAMS, Latin American Screening Study, funded by European Commission, INCO-DEV contract ICA4-CT-2001-10013

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America : the ESTAMPA screening study protocol

Q1Q1Introduction Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. Methods and analysis Women aged 30–64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT01881659Revista Internacional - Indexad

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Bacteriología de la fiebre tifoidea (Laboratorio Bacteriológico de la Asistencia Pública): Tesis para el doctorado

A la cabeza de portada: Universidad Nacional de Buenos Aires. Facultad de Ciencias Médicas. - Incluye nómina de Catedráticos y Asignaturas. Tesis con dedicatoria

Efecto de nanopartículas arqueolipídicas en células endoteliales humanas

The same as liposomes, archaeosomes are nanoparticles (NPs), made of archaeolipids employed as drug delivery systems. Up to date, the effect of archaeosomes on the vascular endothelium, critical data for its admission to the clinic, remains largely unknown. In this study we analyzed the effect of new archaeosomes prepared from a hyperhalophilic strain from Patagonia Argentina on human umbilical vein endothelial cells (HUVECs) under physiological and inflammatory conditions and compare it with that of conventional liposomes. Although none of the NPs affected the viability and expression of ICAM-1 and E-selectin under basal conditions, the archaeosomes reduced the expression of both molecules and the secretion of IL-6 induced by LPS and Pam3CSK4, an effect not observed with TNF- α and associated with an inhibition in the activation of the NF-kB and ERK1/2 pathway. None of these parameters were modified by the liposomes. Similarly, only archaeosomes were endocytosed by HUVECs.Our data reveal an important capacity of these archaeosomes to decrease endothelial activation andsuggest that loaded with anti-inflammatory drugs, they could magnify their activity on inflamed endothelium, their research in vasculopathies being of special interest.Igual que los liposomas, los arqueosomas son nanopartículas (NPs), utilizadas como sistemas de liberación de fármacos. Los arqueosomas son liposomas preparados con arqueolípidos; sin embargo, su efecto sobre el endotelio vascular, datos cruciales para su ingreso en la clínica, es desconocido. En este estudio analizamos el efecto de nuevos arqueosomas preparados a partir de una cepa hiperhalófila de la Patagonia Argentina en células endoteliales de vena umbilical humana (HUVECs) en condiciones fisiológicas e inflamatorias y lo comparamos con el de liposomas convencionales. Si bien ninguna de las NPs afectó la viabilidad y expresión de ICAM-1 y E-selectina en condiciones basales, los arqueosomas redujeron la expresión de ambas moléculas y la secreción de IL-6 inducida por LPS y Pam3CSK4, efecto no observado con TNF-α y asociado a una inhibición en la activación de la vía NF-kB y ERK1/2.Ninguno de estos parámetros fue modificado por los liposomas. En forma similar, solamente los arqueosomas fueron endocitados por HUVECs.Nuestros datos revelan una importante capacidad de estos arqueosomas para disminuir la activación endotelial y sugieren que, cargados con drogas antiinflamatorias, podrían magnificar su actividad sobre el endotelio inflamado siendo de especial interés su investigación en vasculopatías

The Anti-Inflammatory Effect of Nanoarchaeosomes on Human Endothelial Cells

Archaebacterias are considered a unique source of novel biomaterials of interest for nanomedicine. In this perspective, the effects of nanoarchaeosomes (ARC), which are nanovesicles prepared from polar lipids extracted from the extreme halophilic Halorubrum tebenquinchense, on human umbilical vein endothelial cells (HUVEC) were investigated in physiological and under inflammatory static conditions. Upon incubation, ARC (170 nm mean size, −41 mV ζ) did not affect viability, cell proliferation, and expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin under basal conditions, but reduced expression of both molecules and secretion of IL-6 induced by lypopolysaccharide (LPS), Pam3CSK4 or Escherichia coli. Such effects were not observed with TNF-α or IL-1β stimulation. Interestingly, ARC significantly decreased basal levels of von Willebrand factor (vWF) and levels induced by all stimuli. None of these parameters was altered by liposomes of hydrogenated phosphatidylcholine and cholesterol of comparable size and concentration. Only ARC were endocytosed by HUVEC and reduced mRNA expression of ICAM-1 and vWF via NF-ĸB and ERK1/2 in LPS-stimulated cells. This is the first report of the anti-inflammatory effect of ARC on endothelial cells and our data suggest that its future use in vascular disease may hopefully be of particular interest

Cost-effectiveness of quadrivalent vaccine against human papilloma virus in Argentina based on a dynamic transmission model

Objective. To assess the cost-effectiveness of the qua- drivalent vaccine against human papillomavirus (HPV) in Argentina from the health system perspective. Materials and methods. A dynamic transmission model was used to estimate the impact of the vaccine on the incidence of cervical cancer, warts, and other HPV related diseases; in quality adjusted life years (QALYs); and in healthcare costs. Results. Vaccination could reduce the risk of cervical cancer by 60% and by 67% the risk of genital warts. Compared to a non-vaccine scenario, the immunization strategy showed an incremental benefit of 0.00234 QALY per person at an incremental cost of US$2.36, resulting in an incremental cost-effectiveness ratio of US$1007.55 per QALY gained. Sensitivity analysis proved the robustness of these results. Conclusions. Immunization with the quadrivalent vaccine was a cost-effective intervention in Argentina, and it was far below the threshold of one gross domestic product per capita (US$15 009) per QALY gained

Effect of archaeolipid nanoparticles on human endothelial cells

Igual que los liposomas, los arqueosomas son nanopartículas (NPs), utilizadas como sistemas de liberación de fármacos. Los arqueosomas son liposomas preparados con arqueolípidos; sin embargo, su efecto sobre el endotelio vascular, datos cruciales para su ingreso en la clínica, es desconocido. En este estudio analizamos el efecto de nuevos arqueosomas preparados a partir de una cepa hiperhalófila de la Patagonia Argentina en células endoteliales de vena umbilical humana (HUVECs) en condiciones fisiológicas e inflamatorias y lo comparamos con el de liposomas convencionales. Si bien ninguna de las NPs afectó la viabilidad y expresión de ICAM-1 y E-selectina en condiciones basales, los arqueosomas redujeron la expresión de ambas moléculas y la secreción de IL-6 inducida por LPS y Pam3CSK4, efecto no observado con TNF-α y asociado a una inhibición en la activación de la vía NF-kB y ERK1/2. Ninguno de estos parámetros fue modificado por los liposomas. En forma similar, solamente los arqueosomas fueron endocitados por HUVECs. Nuestros datos revelan una importante capacidad de estos arqueosomas para disminuir la activación endotelial y sugieren que, cargados con drogas antiinflamatorias, podrían magnificar su actividad sobre el endotelio inflamado siendo de especial interés su investigación en vasculopatías.The same as liposomes, archaeosomes are nanoparticles (NPs), made of archaeolipids employed as drug delivery systems. Up to date, the effect of archaeosomes on the vascular endothelium, critical data for its admission to the clinic, remains largely unknown. In this study we analyzed the effect of new archaeosomes prepared from a hyperhalophilic strain from Patagonia Argentina on human umbilical vein endothelial cells (HUVECs) under physiological and inflammatory conditions and compare it with that of conventional liposomes. Although none of the NPs affected the viability and expression of ICAM-1 and E-selectin under basal conditions, the archaeosomes reduced the expression of both molecules and the secretion of IL-6 induced by LPS and Pam3CSK4, an effect not observed with TNF- α and associated with an inhibition in the activation of the NF-kB and ERK1/2 pathway. None of these parameters were modified by the liposomes. Similarly, only archaeosomes were endocytosed by HUVECs. Our data reveal an important capacity of these archaeosomes to decrease endothelial activation and suggest that loaded with anti-inflammatory drugs, they could magnify their activity on inflamed endothelium, their research in vasculopathies being of special interest.Fil: Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Jerez, Horacio Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; ArgentinaFil: Tatti, Silvio Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Diseño de Estrategias de Targeting de Drogas; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin