SARS-CoV-2 Variants and Clinical Outcomes: A Systematic Review.

BACKGROUND: From the start of the COVID-19 pandemic, new SARS-CoV-2 variants have emerged that potentially affect transmissibility, severity, and immune evasion in infected individuals. In the present systematic review, the impact of different SARS-CoV-2 variants on clinical outcomes is analyzed. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Two databases (PubMed and ScienceDirect) were searched for original articles published from 1 January 2020 to 23 November 2021. The articles that met the selection criteria were appraised according to the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Thirty-three articles were included, involving a total of 253,209 patients and 188,944 partial or complete SARS-CoV-2 sequences. The most reported SARS-CoV-2 variants showed changes in the spike protein, N protein, RdRp and NSP3. In 28 scenarios, SARS-CoV-2 variants were found to be associated with a mild to severe or even fatal clinical outcome, 15 articles reported such association to be statistically significant. Adjustments in eight of them were made for age, sex and other covariates. CONCLUSIONS: SARS-CoV-2 variants can potentially have an impact on clinical outcomes; future studies focused on this topic should consider several covariates that influence the clinical course of the disease.

SARS-CoV-2 Reinfection among Healthcare Workers in Mexico: Case Report and Literature Review.

Since the onset of the COVID-19 pandemic, there have been multiple questions regarding reinfections associated with SARS-CoV-2. Healthcare workers on duty, due to overexposure in environments where there are more cases of COVID-19, are more prone to become infected by this virus. Here, we report 4 cases that meet the definition of clinical reinfection by SARS-CoV-2, as well as a literature review on this subject; all occurred in healthcare workers in Acapulco Guerrero, Mexico who provide their services in a hospital that cares for patients with COVID-19. The time between the manifestation of the first and second infection for each case was 134, 129, 107 and 82 days, all patients presented symptomatology in both events. The time between remission of the first infection and onset of second infection was 108, 109, 78 and 67 days for each case, while the time to confirmation by reverse transcription polymerase chain reaction (RT-PCR) between infections was 134, 124, 106 and 77 days. In two of the four cases the reinfection resulted in a more severe case, while in the remaining two cases the manifestation of symptoms and complications was similar to that presented in the first infection. Given this scenario, greater care is needed in the management of the pandemic caused by SARS-CoV-2 to protect healthcare workers and the general public from risks and complications caused by a possible reinfection by SARS-CoV-2.

Benefit of double-reading cytology smears as a triage strategy among high-risk human papillomavirus-positive women in Mexico.

BACKGROUND: The goal of this study was to determine whether the detection of histologically confirmed cases of cervical high-grade squamous intraepithelial lesions or worse (HSIL+) can be increased by having each liquid-based cytology (LBC) slide read by 2 cytotechnologists as part of routine screening. METHODS: Over 36,212 women aged 30 to 64 years participated in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) Study in Mexico between 2013 and 2016. For each participant, 2 cervical samples were collected at the same clinic visit, one to test for high-risk human papillomavirus (hrHPV) and the other for LBC, which was used to triage those with a hrHPV positive result. LBC slides were evaluated by 7 cytotechnologists, with each slide read independently by 2 blinded cytotechnologists. All women with atypical cells of undetermined significance or a worse result were referred to colposcopy for further evaluation and diagnosis. Three pathologists evaluated the biopsy specimens to confirm the final HSIL+ diagnosis. The HSIL+ detection rates for the single versus double reading were estimated and compared. RESULTS: A total of 3,914 women with a positive hrHPV result were triaged with LBC. The first and second cytology readings resulted in 43 HSIL+ cases detected; the double-reading strategy detected 9 additional HSIL+ cases, resulting in a total of 52 HSIL+ cases. The HSIL+ detection rate increased from 10.99/1000 with a single reading to 13.29/1000 with the double-reading strategy (P = .004). CONCLUSION: A 20.9% increase in HSIL+ cases detected was achieved with a double reading of the LBC slides in this sample of hrHPV-positive women.

Peer-Review and Rejection Causes in Submitting Original Medical Manuscripts.

The purpose of specialized medical journals is to accurately disseminate the results of new research. The peer-review process is crucial for journals to be able to fulfill this purpose. Although the peer-review determines whether scientific papers are accepted or rejected for publication, for many authors is a not well known process in its entirety. Many journals have focused on educating their audience about how and what is assessed during peer-review, nevertheless, the rate of manuscripts rejected because of easily-avoidable causes related to this, remains high. In this paper, we describe the process that specialized journals use to assess original medical manuscripts and list the main causes of paper rejection. Practicing physicians and medical students who wish to report their research results stand to benefit if they can identify and early avoid on the issues that most often arise during the peer-review process.

From the handling of an outbreak by an unknown pathogen in Wuhan to the preparedness and response in the face of the emergence of Covid-19 in Mexico.

On December 31, 2019, the Chinese health authorities informed the international community, through the mechanisms established by the World Health Organization (WHO), of a pneumonia epidemic of unknown etiology in Wuhan, Hubei Province. The first cases were reported early in that month and were linked to a history of having visited a market where food and live animals are sold. On January 7, 2020, isolation and identification of the culprit pathogen was achieved using next-generation sequencing, while the number of affected subjects continued to rise. The publication of full-genomes of the newly identified coronavirus (initially called 2019-nCoV, now called SARS-CoV2) in public and private databases, of standardized diagnostic protocols and of the clinical-epidemiological information generated will allow addressing the Public Health Emergency of International Concern (PHEIC), declared on January 30 by the WHO. With this document, we intend to contribute to the characterization of the pneumonia epidemic, now designated coronavirus disease (Covid-19) review the strengths Mexico has in the global health concert and invite health professionals to join the preparedness and response activities in the face of this emergency.

El 31 de diciembre de 2019, las autoridades chinas de salud informaron a la comunidad internacional, a través de los mecanismos establecidos por la Organización Mundial de la Salud (OMS), de una epidemia de neumonía con etiología desconocida en Wuhan, provincia de Hubei. Los primeros casos se notificaron a inicios de ese mes y se vincularon al antecedente de visitar un mercado de comida y animales vivos. El 7 de enero de 2020 se logró el aislamiento y reconocimiento del patógeno responsable mediante secuenciación de siguiente generación, mientras el número de afectados continuaba en ascenso. La publicación de genomas completos del nuevo coronavirus identificado (inicialmente denominado 2019-nCoV, ahora designado SARS-CoV2) en bases de datos públicas y privadas, de protocolos diagnósticos estandarizados y de la información clínica epidemiológica generada permitirá atender la Emergencia de Salud Pública de Importancia Internacional (ESPII) declarada el 30 de enero por la OMS. Con este documento pretendemos aportar a la caracterización de la epidemia de neumonía, ahora llamada enfermedad por coronavirus (Covid-19), revisar las fortalezas que tiene México en el concierto de la salud global e invitar a los profesionales de la salud a incorporarse a las actividades de preparación y respuesta ante esta emergencia.

De la atención de un brote por un patógeno desconocido en Wuhan hasta la preparación y respuesta ante la emergencia de Covid-19 en México / From the handling of an outbreak by an unknown pathogen in Wuhan to the preparedness and response in the face of the emergence of Covid-19 in Mexico

Resumen El 31 de diciembre de 2019, las autoridades chinas de salud informaron a la comunidad internacional, a través de los mecanismos establecidos por la Organización Mundial de la Salud (OMS), de una epidemia de neumonía con etiología desconocida en Wuhan, provincia de Hubei. Los primeros casos se notificaron a inicios de ese mes y se vincularon al antecedente de visitar un mercado de comida y animales vivos. El 7 de enero de 2020 se logró el aislamiento y reconocimiento del patógeno responsable mediante secuenciación de siguiente generación, mientras el número de afectados continuaba en ascenso. La publicación de genomas completos del nuevo coronavirus identificado (inicialmente denominado 2019-nCoV, ahora designado SARS-CoV2) en bases de datos públicas y privadas, de protocolos diagnósticos estandarizados y de la información clínica epidemiológica generada permitirá atender la Emergencia de Salud Pública de Importancia Internacional (ESPII) declarada el 30 de enero por la OMS. Con este documento pretendemos aportar a la caracterización de la epidemia de neumonía, ahora llamada enfermedad por coronavirus (Covid-19), revisar las fortalezas que tiene México en el concierto de la salud global e invitar a los profesionales de la salud a incorporarse a las actividades de preparación y respuesta ante esta emergencia.

Abstract On December 31, 2019, the Chinese health authorities informed the international community, through the mechanisms established by the World Health Organization (WHO), of a pneumonia epidemic of unknown etiology in Wuhan, Hubei Province. The first cases were reported early in that month and were linked to a history of having visited a market where food and live animals are sold. On January 7, 2020, isolation and identification of the culprit pathogen was achieved using next-generation sequencing, while the number of affected subjects continued to rise. The publication of full-genomes of the newly identified coronavirus (initially called 2019-nCoV, now designated SARS-CoV2) in public and private databases, of standardized diagnostic protocols and of the clinical-epidemiological information generated will allow addressing the Public Health Emergency of International Concern (PHEIC), declared on January 30 by the WHO. With this document, we intend to contribute to the characterization of the pneumonia epidemic, now called Corona virus disease (Covid-19) review the strengths Mexico has in the global health concert and invite health professionals to join the preparedness and response activities in the face of this emergency.

Errores más comunes al redactar artículos médicos originales.

One of the skills that is more in need to be strengthened in the medical area is the dissemination of knowledge. For this reason, it is necessary to provide elements that promote training in scientific writing. Identifying the most common problems when writing medical original articles for publication will provide useful resources that should contribute to the generation of knowledge. There are multiple reasons that intervene for an original article not to be accepted in a medical journal, among which failure to follow instructions for authors and methodological, design and structural problems stand out. However, the aspect that most influences and that is seldom pointed out, is inadequate writing of research manuscripts, which becomes evident in the different sections that make up manuscripts. All the above-mentioned factors are the responsibility of the authors, and therefore must be taken care of properly. The purpose of this article is to identify the most common mistakes when writing original medical manuscripts, which, if avoided, will increase the possibility for research papers to be accepted for publication.

Una de las habilidades que más requiere ser fortalecida en el área médica es la difusión de conocimiento, por tal motivo, es necesario brindar elementos que promuevan la capacitación en redacción científica. Identificar cuáles son los problemas más comunes al redactar artículos médicos originales para su publicación proporcionará recursos útiles que contribuyan a la generación de conocimiento. Existen diversos motivos que intervienen para que un artículo original no sea aceptado en una revista médica, entre los que destacan falta de apego a las instrucciones para autores, problemas metodológicos y de diseño, así como de estructura, sin embargo, el aspecto que más influye y pocas veces se señala, es la redacción inadecuada de los escritos de investigación, la cual se hace patente en las diferentes secciones que componen los manuscritos. Todos los factores mencionados son responsabilidad de los autores, por lo que deben ser atendidos apropiadamente. El presente escrito tiene como objetivo señalar los errores más comunes al redactar escritos médicos originales, los cuales, de ser evitados, incrementarán la posibilidad de que sus trabajos de investigación sean aceptados para su publicación.

Methylation estimates the risk of precancer in HPV-infected women with discrepant results between cytology and HPV16/18 genotyping.

BACKGROUND: Vigilant management of women with high-risk human papillomavirus (hrHPV) is necessary in cancer screening programs. To this end, we evaluated the performance of S5 (targeting DNA methylation in HPV16, HPV18, HPV31, HPV33, and human gene EPB41L3) to predict cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in a sample of hrHPV-infected women referred to colposcopy in the FRIDA Study, a large screening trial in Mexico. A nested case-control sample with women referred to colposcopy either by atypical squamous cells of undetermined significance or higher (ASCUS+) in cytology and/or positive for HPV types 16 or 18 was tested by S5. Seventy-nine cases of CIN2+ were age-matched to 237 controls without a diagnosis of CIN2+ (

Triage strategies in cervical cancer detection in Mexico: methods of the FRIDA Study.

OBJECTIVE: This paper describes the study design and baseline characteristics of the study population, including the first 30 829 women who enrolled in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA Study). This is a large population based study that is evaluating the performance and cost-effectiveness of different triage strategies for high-risk HPV (hrHPV) positive women in Mexico. MATERIALS AND METHODS: The target population is more than 100 000 women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico. Since August 2013, all women in the region have been invited to enroll in the study. The study participants are evaluated to determine hrHPV infection using the Cobas 4800 HPV test. The HPV-16/18 genotyping and cytology triage strategies are performed as reflex tests in all hrHPV-positive participants. Women with a positive HPV-16/18 test and/or abnormal cytology (atypical squamous cells of undetermined significance or worse, ASCUS+) are referred for colposcopy evaluation, where a minimum of four biopsies and an endocervical sample are systematically collected. Histologic confirmation is performed by a standardized panel of pathologists. RESULTS: Among the 30 829 women who have been screened, the overall prevalence of hrHPV is 11.0%. The overall prevalence of HPV16 and HPV18 are 1.5% and 0.7%, respectively. Cytological abnormalities (ASCUS+) were detected in 11.8% of the hrHPV-positive women. A total of 27.0% (920/3,401) of the hrHPV-positive women were referred to colposcopy because of a positive HPV16/18 test and/or abnormal reflex cytology, (31.6% had only ASCUS+, 53.6% were HPV16/18 positive with a normal cytology result, and 9.5% were positive to both triage tests). CONCLUSION: The results of this study will help policy makers and health service providers establish the best practices for triage in cervical cancer screening in Mexico and other countries.

Triage strategies in cervical cancer detection in Mexico: methods of the FRIDA Study / Estrategias de triage en la detección de cáncer cervical: métodos del estudio FRIDA

Abstract Objective: This paper describes the study design and baseline characteristics of the study population, including the first 30 829 women who enrolled in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA Study). This is a large population based study that is evaluating the performance and cost-effectiveness of different triage strategies for high-risk HPV (hrHPV) positive women in Mexico. Materials and methods: The target population is more than 100 000 women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico. Since August 2013, all women in the region have been invited to enroll in the study. The study participants are evaluated to determine hrHPV infection using the Cobas 4800 HPV test. The HPV-16/18 genotyping and cytology triage strategies are performed as reflex tests in all hrHPV-positive participants. Women with a positive HPV-16/18 test and/or abnormal cytology (atypical squamous cells of undetermined significance or worse, ASCUS+) are referred for colposcopy evaluation, where a minimum of four biopsies and an endocervical sample are systematically collected. Histologic confirmation is performed by a standardized panel of pathologists. Results: Among the 30 829 women who have been screened, the overall prevalence of hrHPV is 11.0%. The overall prevalence of HPV16 and HPV18 are 1.5% and 0.7%, respectively. Cytological abnormalities (ASCUS+) were detected in 11.8% of the hrHPV-positive women. A total of 27.0% (920/3,401) of the hrHPV-positive women were referred to colposcopy because of a positive HPV16/18 test and/or abnormal reflex cytology, (31.6% had only ASCUS+, 53.6% were HPV16/18 positive with a normal cytology result, and 9.5% were positive to both triage tests). Conclusion: The results of this study will help policy makers and health service providers establish the best practices for triage in cervical cancer screening in Mexico and other countries.

Resumen Objetivo: El objetivo de este artículo es describir el diseño del estudio FRIDA y las características basales de las primeras 30 829 mujeres tamizadas. El estudio FRIDA (Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage) es un estudio de demostración con base poblacional diseñado para evaluar el desempeño y costo-efectividad de diferentes alternativas de triage en mujeres VPH de alto riesgo (VPHar) positivas bajo condiciones reales de un programa de tamizaje para cáncer cervical en México. Material y métodos: La población objetivo la conforman poco más de 100 000 mujeres de 30 a 64 años que asisten al programa de detección oportuna de cáncer cervical en alguno de los 100 centros de salud de la jurisdicción sanitaria 1 de Tlaxcala. Desde agosto de 2013, todas las mujeres son invitadas al estudio. Las participantes del estudio son tamizadas para determinar la infección con VPHar mediante la prueba VPHar Cobas 4800. Se realizan las pruebas de triage de tipificación de VPH16/18 y citología en todas las mujeres con resultados VPHar positivos. Las mujeres con un resultado positivo a VPH16/18 y/o citología anormal (células escamosas atípicas de resultado incierto o peor: ASCUS+) son referidas a evaluación colposcópica, seguida de una colección sistemática de un mínimo de cuatro biopsias cervicales y un cepillado endocervical. La confirmación histológica se lleva a cabo por un panel de patólogos. Resultados Un total de 30 829 mujeres han sido tamizadas, con una prevalencia de VPHar del 11.0%. La prevalencia global de VPH16 y VPH18 es 1.5% y 0.7%, respectivamente. Se detectó un 11.8% de anormalidades citológicas (ASCUS+). Entre las mujeres VPHar positivas, la prevalencia de un resultado de triage positivo (VPH16/18 o citología anormal) fue 27.0%, distribuido de la siguiente forma, 31.6% de éstos fueron sólo ASCUS+ VPH16/18 negativo, 53.6% fueron VPH 16/18 positivos y citología normal, y 9.5% positivos a ambas pruebas de triage. Conclusión: Los resultados de este estudio ayudarán tanto a los tomadores de decisiones como a los proveedores de servicios de salud a establecer la mejor estrategia de triage en programas de tamizaje de cáncer cervical basados en VPHar en México y en otros países.

Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis.

Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.