Resección hepática laparoscópica versus hepatectomía abierta para lesiones benignas: estudio comparativo con propensity score matching / Laparoscopic liver resection versus open liver resection for benign lesions: a comparative study with propensity score matching

RESUMEN Antecedentes : las ventajas de la hepatectomía videolaparoscópica (HVL) hicieron que gane cada vez más campo para el tratamiento de los tumores hepáticos benignos (THB). Objetivo : comparar los resultados perioperatorios de pacientes sometidos a HVL con los de los operados con hepatectomía abierta (HA) por THB, emparejados con propensity score matching (PSM). Material y métodos : estudio descriptivo, retrospectivo y comparativo de HA y HVL por THB entre agosto de 2010 y junio de 2021. Se analizaron variables demográficas, preoperatorias, intraoperatorias y posoperatorias. Para evitar sesgos de las distintas covariables entre los grupos se realizó un PSM 1:1. Resultados : de 403 hepatectomías, se analizaron 82 por THB. De ellas 36 (44%) fueron HA y 46 (56%) HVL. Edad media 45 ±14 años, 65% mujeres. Tras realizar el PSM, quedaron dos grupos de 28 pacientes cada uno. En HA, 5 (18%) pacientes requirieron transfusiones y ninguno en HVL (p = 0,01). Las complicaciones mayores se presentaron en 4 (14%) pacientes en HA, y ninguna en HVL (p = 0,03). Se reoperaron 4 (14%) pacientes con HA y ningún paciente con HVL (p = 0,03). La estadía hospitalaria total fue significativamente mayor en las HA (p = 0,04). No se registraron muertes a los 90 días en ninguno de los dos grupos. Conclusión : la HVL por THB es una técnica segura y eficaz, ya que los pacientes presentaron menor requerimiento transfusional, número de reoperaciones, de complicaciones mayores y de estadía hospitalaria que con HA. Por las ventajas encontradas, la HVL podría ser considerada la técnica de elección en cirugía por THB.

ABSTRACT Background : The advantages of laparoscopic liver resection (LLR) have increased its use for the treatment of benign liver tumors (BLTs). Objective : The aim of this study was to compare the perioperative outcomes of patients undergoing LLR with those operated on with open liver resection (OLR) for BLTs using propensity score matching (PSM). Material and methods : We conducted a descriptive and retrospective study comparing OLRs with LLRs performed between August 2010 and June 2021. The demographic, perioperative, intraoperative and postoperative variables were analyzed. We used PSM with 1:1 matching to avoid biases of the different covariates between the groups. Results : Of 303 liver resections, 82 corresponded to BLTs and were included in the analysis; 36 (44%) were OLRs and 46 (56%) were LLRs. Mean age was 45 ±14 years and 65% were women. After PSM, two groups of 28 patients each were constituted. Five patients (18%) in the OLR group and none in the LLR required transfusions (p = 0.01). Major complications, occurred in 4 (14%) patients in the OLR group and in no cases in the LLR group (p = 0.03). Four (14%) undergoing OLR required reoperation versus no patients with LLR (p = 0.03). Total length of hospital stay was significantly longer in OLR (p = 0.04). There were no deaths in any of the groups within 90 days. Conclusion : LLR for BLTs is a safe and effective technique, with lower requirement for transfusions, fewer reoperations and major complications and shorter length of hospital stay than OLR, Therefore, LLR could be considered the surgical technique of choice for BLTs.

SNPs Sets in Codifying Genes for Xenobiotics-Processing Enzymes Are Associated with COPD Secondary to Biomass-Burning Smoke.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; the main risk factors associated with the suffering are tobacco smoking (TS) and chronic exposure to biomass-burning smoke (BBS). Different biological pathways have been associated with COPD, especially xenobiotic or drug metabolism enzymes. This research aims to identify single nucleotide polymorphisms (SNPs) profiles associated with COPD from two expositional sources: tobacco smoking and BBS. One thousand-five hundred Mexican mestizo subjects were included in the study and divided into those exposed to biomass-burning smoke and smokers. Genome-wide exome genotyping was carried out using Infinium Exome-24 kit arrays v. 1.2. Data quality control was conducted using PLINK 1.07. For clinical and demographic data analysis, Rstudio was used. Eight SNPs were found associated with COPD secondary to TS and seven SNPs were conserved when data were analyzed by genotype. When haplotype analyses were carried out, five blocks were predicted. In COPD secondary to BBS, 24 SNPs in MGST3 and CYP family genes were associated. Seven blocks of haplotypes were associated with COPD-BBS. SNPs in the ARNT2 and CYP46A1 genes are associated with COPD secondary to TS, while in the BBS comparison, SNPs in CYP2C8, CYP2C9, MGST3, and MGST1 genes were associated with increased COPD risk.

Factors influencing mortality trends of pancreatic cancer in Spain, 1955-2020

Objectives: The aim of this study was to analyze the trends of pancreatic cancer mortality in Spain from 1955-2020 in both genders and every age group, in order to describe the changes in the prevalence of some risk factors and their possible influence on mortality.Methods: Direct standardized mortality rates were calculated using the World Standard Population 2000-2025 and Joinpoint analysis was performed for age-specific and age-standardized mortality trends for the period from 1955-2020.Results: Mortality rates increased with age in both genders, with a marked increase in older groups. During 2020, 71.5% of male deaths and 81.5% of female deaths from pancreatic cancer occurred among those aged 65 years or more. Spanish National Health Surveys since 1987 show decreasing trends in daily smoking, but striking increases in obesity and diabetes mellitus rates in both genders, and rates of daily smoking and obesity are remarkably higher among disadvantaged social classes.Conclusions: Pancreatic cancer mortality rates have increased uninterruptedly in Spain during the last decades. Increasing trends in obesity and diabetes mellitus, particularly among males, and the different prevalence of obesity and smoking according to social class are public health problems of great concern. Smoking and obesity are potentially avoidable risk factors. Thus, educational programs and legislative measures should be implemented more widely, such as programs for smoking prevention, healthy nutrition and physical exercise, and would be applied more intensively in the most disadvantaged social classes. (AU)

La telesimulación como método de enseñanza clínica en estudiantes de grado de la asignatura "Cirugía". Evaluación cualitativa de una experiencia piloto / Telesimulation as a method of clinical teaching in undergraduate students of surgery. A qualitative evaluation of a pilot experience

RESUMEN Antecedentes: la actual pandemia causada por COVID-19 plantea desafíos a la enseñanza clínica al afectar el desarrollo normal de las actividades presenciales. Se necesitan soluciones que ayuden a mitigar esos efectos. Objetivo: el propósito de este estudio es presentar una estrategia de telesimulacion (TS) y analizar la perspectiva del diseño instruccional desde los estudiantes de grado de Cirugía. Material y métodos: 26 estudiantes tuvieron una inmersión en escenarios de alta fidelidad a distancia, a través de una plataforma de videoconferencia que les permitió experimentar y analizar situaciones críticas y tomar decisiones terapéuticas. El análisis de los datos se realizó desde un abordaje cuantitativo-cualitativo poniendo el foco en las vivencias de los participantes a partir de la encuesta de satisfacción, las transcripciones del debriefing (etapa reflexiva) y una pregunta abierta sobre percepción de aprendizaje, con el propósito de analizar la actividad en torno a las oportunidades de aprendizaje de razonamiento clínico y habilidades no técnicas como también los atributos del método percibidos por los estudiantes. Resultados: todos recomendarían la actividad a otro. Durante la etapa de debriefing emergen aspectos del rendimiento en relación con la hipótesis diagnóstica, la investigación complementaria, el tratamiento y las habilidades no técnicas. Además existió una percepción de aprendizaje más allá de la que ofrece la lectura de contenidos. Conclusión: la TS como oportunidad de aprendizaje favorece la enseñanza clínica. Como técnica, si bien puede lograr alta fidelidad, no puede descuidar los aspectos técnicos y tecnológicos que alterarían su curso.

ABSTRACT Background: The current COVID-19 pandemic poses additional challenges to clinical teaching by affecting the normal development of onsite activities. Solutions are necessary to mitigate these effects. Objective: The aim of this study is to present a telesimulation (TS strategy) and analyze the instructional design perspective of undergraduate students of surgery. Material and methods: Twenty-six students participated in the experience, immersed in high-fidelity virtual scenarios through a video conference platform in which they could experience and analyze critical situations and decide a therapeutic plan. Data analysis was carried out using a quantitative-qualitative approach, focusing on the participants' experiences reported in a satisfaction survey, debriefing transcriptions (reflective stage) and an open-ended question about the perception of learning aimed at analyzing the activity in terms of the opportunities to learn clinical reasoning, non-technical skills and the attributes of the method as perceived by the students. Results: All the students would recommend the activity to another peer. During debriefing, the aspects of performance related with the diagnostic hypothesis, complementary investigation, treatment and non-technical skills emerge. Furthermore, there was a perception of learning beyond that offered by content reading. Conclusion : Telesimulation as a learning opportunity favors clinical teaching. Although TS can achieve high fidelity as a technique, it cannot neglect the technical and technological aspects that would alter its course.

Factors influencing mortality trends of pancreatic cancer in Spain, 1955-2020.

OBJECTIVES: The aim of this study was to analyze the trends of pancreatic cancer mortality in Spain from 1955-2020 in both genders and every age group, in order to describe the changes in the prevalence of some risk factors and their possible influence on mortality. METHODS: Direct standardized mortality rates were calculated using the World Standard Population 2000-2025 and Joinpoint analysis was performed for age-specific and age-standardized mortality trends for the period from 1955-2020. RESULTS: Mortality rates increased with age in both genders, with a marked increase in older groups. During 2020, 71.5% of male deaths and 81.5% of female deaths from pancreatic cancer occurred among those aged 65 years or more. Spanish National Health Surveys since 1987 show decreasing trends in daily smoking, but striking increases in obesity and diabetes mellitus rates in both genders, and rates of daily smoking and obesity are remarkably higher among disadvantaged social classes. CONCLUSIONS: Pancreatic cancer mortality rates have increased uninterruptedly in Spain during the last decades. Increasing trends in obesity and diabetes mellitus, particularly among males, and the different prevalence of obesity and smoking according to social class are public health problems of great concern. Smoking and obesity are potentially avoidable risk factors. Thus, educational programs and legislative measures should be implemented more widely, such as programs for smoking prevention, healthy nutrition and physical exercise, and would be applied more intensively in the most disadvantaged social classes.

SERPINE1 rs6092 Variant Is Related to Plasma Coagulation Proteins in Patients with Severe COVID-19 from a Tertiary Care Hospital.

An impaired coagulation process has been described in patients with severe or critical coronavirus disease (COVID-19). Nevertheless, the implication of coagulation-related genes has not been explored. We aimed to evaluate the impact of F5 rs6025 and SERPINE1 rs6092 on invasive mechanical ventilation (IMV) requirement and the levels of coagulation proteins among patients with severe COVID-19. Four-hundred fifty-five patients with severe COVID-19 were genotyped using TaqMan assays. Coagulation-related proteins (P-Selectin, D-dimer, P-selectin glycoprotein ligand-1, tissue plasminogen activator [tPA], plasminogen activator inhibitor-1, and Factor IX) were assessed by cytometric bead arrays in one- and two-time determinations. Accordingly, SERPINE1 rs6092, P-Selectin (GG 385 pg/mL vs. AG+AA 632 pg/mL, p = 0.0037), and tPA (GG 1858 pg/mL vs. AG+AA 2546 pg/mL, p = 0.0284) levels were different. Patients carrying the CT F5-rs6025 genotype exhibited lower levels of factor IX (CC 17,136 pg/mL vs. CT 10,247 pg/mL, p = 0.0355). Coagulation proteins were also different among IMV patients than non-IMV. PSGL-1 levels were significantly increased in the late stage of COVID-19 (>10 days). The frequencies of F5 rs6025 and SERPINE1 rs6092 variants were not different among IMV and non-IMV. The SERPINE1 rs6092 variant is related to the impaired coagulation process in patients with COVID-19 severe.

First-in-human immunoPET imaging of HIV-1 infection using 89Zr-labeled VRC01 broadly neutralizing antibody.

A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases.

Effect of BCG Revaccination on Occupationally Exposed Medical Personnel Vaccinated against SARS-CoV-2.

The production of specific neutralizing antibodies by individuals is thought to be the best option for reducing the number of patients with severe COVID-19, which is the reason why multiple vaccines are currently being administered worldwide. We aimed to explore the effect of revaccination with BCG, on the response to a subsequent anti-SARS-CoV-2 vaccine, in persons occupationally exposed to COVID-19 patients. Two groups of 30 randomized participants were selected: one group received a BCG revaccination, and the other group received a placebo. Subsequently, both groups were vaccinated against SARS-CoV-2. After each round of vaccination, the serum concentration of Th1/Th2 cytokines was determined. At the end of the protocol, neutralizing antibodies were determined and the HLA-DRB loci were genotyped. The participants from the BCG group and anti-SARS-CoV-2 vaccine group had increased serum cytokine concentrations (i.e., IL-1ß, IL-4, IL-6, IL-12p70, IL-13, IL-18, GM-CSF, INF-γ, and TNF-α) and higher neutralizing antibody titers, compared to the group with Placebo-anti-SARS-CoV-2. Twelve HLA-DRB1 alleles were identified in the Placebo-anti-SARS-CoV-2 group, and only nine in the group revaccinated with BCG. The DRB1*04 allele exhibited increased frequency in the Placebo-anti-SARS-CoV-2 group; however, no confounding effects were found with this allele. We conclude that revaccination with BCG synergizes with subsequent vaccination against SARS-CoV-2 in occupationally exposed personnel.

Differential Genomic Profile in TERT, DSP, and FAM13A Between COPD Patients With Emphysema, IPF, and CPFE Syndrome.

Background: Genetic association studies have identified single nucleotide polymorphisms (SNPs) associated with lasting lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF), as well as the simultaneous presentation, known as Combined Pulmonary Fibrosis and Emphysema (CPFE) Syndrome. It is unknown if these diseases share genetic variants previously described in an independent way. This study aims to identify common or differential variants between COPD, IPF, and CPFE. Materials and methods: The association analysis was carried out through a case-control design in a Mexican mestizo population (n = 828); three patients' groups were included: COPD smokers (COPD-S, n = 178), IPF patients (n = 93), and CPFE patients (n = 16). Also, two comparison groups were analyzed: smokers without COPD (SWOC, n = 367) and healthy subjects belonging to the Mexican Pulmonary Aging Cohort (PAC, n = 174). Five SNPs in four genes previously associated to interstitial and obstructive diseases were selected: rs2609255 (FAM13A), rs2736100 (TERT), rs2076295 (DSP) rs5743890, and rs111521887 (TOLLIP). Genotyping was performed by qPCR using predesigned Taqman probes. Results: In comparing IPF vs. PAC, significant differences were found in the frequency of the rs260955 G allele associated with the IPF risk (OR = 1.68, p = 0.01). Also, the genotypes, GG of rs260955 (OR = 2.86, p = 0.01) and TT of rs2076295 (OR = 1.79, p = 0.03) were associated with an increased risk of IPF; after adjusting by covariables, only the rs260955 G allele remain significant (p = 0.01). For the CPFE vs. PAC comparison, an increased CPFE risk was identified since there is a difference in the rs2736100 C allele (OR = 4.02, p < 0.01; adjusted p < 0.01). For COPD-S, the rs2609255 TG genotype was associated with increased COPD risk after adjusting by covariables. Conclusion: The rs2736100 C allele is associated with decreased IPF risk and confers an increased risk for CPFE. Also, the rs2076295 TT genotype is associated with increased IPF risk, while the GG genotype is associated with CFPE susceptibility. The rs2609255 G allele and GG genotype are associated with IPF susceptibility, while the TG genotype is present in patients with emphysema.

Experiencia inicial en hepatectomías videolaparoscópicas / Initial experience in laparoscopic liver resections

RESUMEN Antecedentes: La cirugía hepática videolaparoscópica ha experimentado un importante desarrollo; sin embargo, la mayoría de las hepatectomías continúan haciéndose por vía convencional. Objetivo: presentar la experiencia y aplicabilidad de hepatectomías videolaparoscópicas. Material y métodos: análisis retrospectivo de pacientes sometidos a una hepatectomía entre agosto de 2010 y diciembre de 2019. Analizamos variables preoperatorias, intraoperatorias y posoperatorias. Para evaluar la aplicabilidad, se dividió la muestra en: Etapa 1: agosto de 2010 a diciembre de 2013; Etapa 2: enero de 2014 a diciembre de 2016, Etapa 3: enero de 2017 a diciembre de 2019. Resultados: de 385 hepatectomías realizadas, 119 fueron videolaparoscópicas: 53 (44%) fueron to talmente laparoscópicas, 64 (54%) mano-asistidas y 2 híbridas. La aplicabilidad global fue 31%. En la etapa 1: 23% , en la 2: 30% y en la 3: 44% (p < 0,05). Fueron patología maligna en la etapa 1: 36%, en la 2: 67% y en la 3: 72% (p < 0,05). Hepatectomías mayores: 13%, 31% y 32% en etapas 1, 2, y 3, respectivamente (p < 0,05). El índice de conversión fue 12%, 0% y 11%, respectivamente (p NS). Se utilizó clampeo pedicular en: 6%, 5% y 45%; (p < 0,05). Las complicaciones en la etapa 1 fueron 30%, en la 2: 28% y en la 3: 17%, siendo complicaciones Dindo-Clavien III o más, el 6%, 13% y 5%, respectivamente, p NS. Conclusiones: Aa pesar de su complejidad, las hepatectomías videolaparoscópicas son técnicamente reproducibles. Adquiriendo experiencia, podemos aumentar la aplicabilidad, a favor de la patología oncológica y complejidad, sin comprometer la seguridad del paciente.

ABSTRACT Background: Despite laparoscopic liver resection has significantly evolved, most hepatectomies are performed by the conventional approach. Objective: The aim of this study is to present the initial experience and applicability of laparoscopic liver resections. Material and methods: We conducted a retrospective analysis of patients undergoing liver resection between August 2010 and December 2019. Perioperative, intraoperative and postoperative variables were analyzed. To evaluate applicability, the sample was divided into 3 stages: stage 1, from August 2010 to December 2013; stage 2, from January 2014 to December 2016; and stage 3, from January 2017 to December 2019. Results: Of 385 liver resections performed, 119 were laparoscopic procedures: 53 (44%) were pure laparoscopic procedures, 64 (54%) were hand-assisted (64 patients) and 2 corresponded to hybrid procedures. Global applicability was 31%. In stage 1 1: 23%, in 2: 30% and in 3: 44% (p < 0.05). Malignant lesions: stage 1: 36%, stage 2: 67% and stage 3: 72% (p < 0.05). Major liver resections: 13%, 31% and 32% in stages 1, 2, and 3, respectively (p < 0.05). Conversion rate was 12%, 0% and 11%, respectively (p NS). Hepatic pedicle clamping was used in 6%, 5% and 45%; (p < 0.05). Complications in stage 1 were 30%, in stage 2: 28% and in stage 3: 17%, and Clavien-Dindo complications grade 3 or greater were 6%, 13% and 5%, respectively, p NS. Conclusions: Laparoscopic liver resections are complex procedures but technically reproducible. Applicability increases with the acquisition of experience, not only in malignant lesions but also in complex lesions ensuring safety for the patient.

Angiotensin-Converting Enzyme 2 (ACE2) in the Context of Respiratory Diseases and Its Importance in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

Angiotensin-Converting Enzyme 2 (ACE2) is an 805 amino acid protein encoded by the ACE2 gene expressed in various human cells, especially in those located in the epithelia. The primary function of ACE2 is to produce angiotensin (1-7) from angiotensin II (Ang II). The current research has described the importance of ACE2 and Ang (1-7) in alternative routes of the renin-angiotensin system (RAS) that promote the downregulation of fibrosis, inflammation, and oxidative stress processes in a great variety of diseases, such as hypertension, acute lung injury, liver cirrhosis, and kidney abnormalities. Investigations into the recent outbreak of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have revealed the importance of ACE2 during infection and its role in recognizing viral binding proteins through interactions with specific amino acids of this enzyme. Additionally, the ACE2 expression in several organs has allowed us to understand the clinical picture related to the infection caused by SARS-CoV-2. This review aims to provide context for the functions and importance of ACE2 with regards to SARS-CoV-2 in the general clinical aspect and its impact on other diseases, especially respiratory diseases.

Protective Role of Genetic Variants in HSP90 Genes-Complex in COPD Secondary to Biomass-Burning Smoke Exposure and Non-Severe COPD Forms in Tobacco Smoking Subjects.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory disease characterized by airflow obstruction, commonly present in smokers and subjects exposed to noxious particles product of biomass-burning smoke (BBS). Several association studies have identified single-nucleotide polymorphisms (SNP) in coding genes related to the heat shock proteins family-genes that codify the heat shock proteins (Hsp). Hsp accomplishes critical roles in regulating immune response, antigen-processing, eliminating protein aggregates and co-activating receptors. The presence of SNPs in these genes can lead to alterations in immune responses. We aimed to evaluate the association of SNPs in the HSP90 gene complex and COPD. METHODS: We enrolled 1549 participants, divided into two comparison groups; 919 tobacco-smoking subjects (cases COPD-TS n = 294 and, controls SWOC n = 625) and 630 chronic exposed to BBS (cases COPD-BBS n = 186 and controls BBES n = 444). We genotyped 2 SNPs: the rs13296 in HSP90AB1 and rs2070908 in HSP90B1. RESULTS: Through the dominant model (GC + CC), the rs2070908 is associated with decreased risk (p < 0.01, OR = 0.6) to suffer COPD among chronic exposed BBS subjects. We found an association between rs13296 GG genotype and lower risk (p = 0.01, OR = 0.22) to suffer severe COPD-TS forms in the severity analysis. CONCLUSIONS: single-nucleotide variants in the HSP90AB1 and HSP90B1 genes are associated with decreased COPD risk in subjects exposed to BBS and the most severe forms of COPD in tobacco-smoking subjects.

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression.

BACKGROUND: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. METHODS: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. RESULTS: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. CONCLUSION: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

Genetic Susceptibility to Antisynthetase Syndrome Associated With Single-Nucleotide Variants in the IL1B Gene That Lead Variation in IL-1ß Serum Levels.

The antisynthetase syndrome (ASSD) is an autoimmune disorder characterized by myositis, arthritis, mechanic's hands, fever, Raynaud phenomenon, and interstitial lung disease (ILD). We aimed to evaluate single-nucleotide polymorphisms in the interleukin 1B (IL1B) gene and their association between ILD with antisynthetase autoantibodies, as well as IL-1ß serum levels. The most frequent antisynthetase autoantibody was anti-Jo1. The most frequent tomographic pattern was non-specific interstitial pneumonia, whereas in the anti-Jo1 subjects, it was organized pneumonia. Anti-Jo1 patients tend to have more significant arthritis, and Raynaud phenomenon have higher levels of creatinine phosphokinase. In the IL1B gene, the GG genotype and G allele of rs1143634 [odds ratio (OR) = 2.21 and OR = 2.60, respectively, p < 0.05] are associated with an increased risk, as well as with the dominant and recessive models (p < 0.05). This finding is maintained after logistic regression analysis adjusting for potential confounding variables (p < 0.05). Subjects with the rs16944/AG heterozygous genotype had higher serum levels of IL-1ß compared to homozygous (p < 0.05). In conclusion, rs1143634 is associated with a higher risk of ASSD. Also, the GA genotype is associated with higher levels of IL-1ß in ASSD patients.

Polymorphisms in Processing and Antigen Presentation-Related Genes and Their Association with Host Susceptibility to Influenza A/H1N1 2009 Pandemic in a Mexican Mestizo Population.

(1) Background: The influenza A/H1N1 pdm09 virus rapidly spread throughout the world. Despite the inflammatory and virus-degradation pathways described in the pathogenesis of influenza A virus (IAV) infection, little is known about the role of the single nucleotide polymorphisms (SNPs) in the genes involved in the processing and antigenic presentation-related mechanisms. (2) Methods: In this case-control study, we evaluated 17 SNPs in five genes (TAP1, TAP2, TAPBP, PSMB8, and PSMB9). One hundred and twenty-eight patients with influenza A/H1N1 infection (INF-P) and 111 healthy contacts (HC) were included; all of them are Mexican mestizo. (3) Results: In allele and genotype comparison, the rs241433/C allele (TAP2), as well as AG haplotype (rs3763365 and rs4148882), are associated with reduced risk for influenza A/H1N1 infection (p < 0.05). On the other hand, the rs2071888G allele (TAPBP) and GG haplotype (rs3763365 and rs9276810) are associated with a higher risk for influenza A/H1N1 infection. In addition, after adjustment for covariates, the association to a reduced risk for influenza A/H1N1 infection remains with rs241433/C allele (p < 0.0001, OR = 0.24, 95% CI = 0.13-0.43), and the association with TAPBP is also maintained with the G allele (p = 0.0095, OR = 1.89, 95% CI = 1.17-3.06) and GG genotype models (p < 0.05, OR = 2.18, 95% CI = 1.27-3.74). (4) Conclusion: The rs241433/C allele and AC genotype (TAP2) and the AG haplotype are associated with a reduced risk for influenza A/H1N1 infection. In addition, the rs2071888/G allele and GG genotype (TAPBP) and the GG haplotype are associated with a higher risk for developing influenza A/H1N1 infection in a Mexican mestizo population.

The SNP rs13147758 in the HHIP Gene Is Associated With COPD Susceptibility, Serum, and Sputum Protein Levels in Smokers.

BACKGROUND: Genetic association studies have identified single nucleotide polymorphisms (SNPs) related to chronic obstructive pulmonary disease (COPD) susceptibility. The aim of this study was to identify HHIP genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican mestizo smokers. MATERIALS AND METHODS: Association analysis was performed by carrying out a case-control study in Mexican mestizo smokers comprised of two groups: tobacco-smoking subjects with COPD (COPD-TS, n = 222) and smokers without COPD (SWOC, n = 333). We evaluated three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene. Allele discrimination was accomplished by qPCR using TaqMan probes, and determination of protein levels in the serum and sputum supernatants (SS) was performed using ELISA. RESULTS: Statistically significant differences were observed in the rs13147758 GG genotype (adjusted p = 0.014, OR = 1.95) and the rs13147758-rs1828591 GA haplotype (p = 6.6E-06, OR = 2.65) in the case-control comparison. HHIP protein levels were elevated in SS samples from the COPD-TS group compared to those from the SWOC group (p = 0.03). Based on genotype analysis, HHIP protein levels were lower in the serum samples of rs13147758 GG genotype carriers in the COPD-TS group than in the serum samples of rs13147758 GG genotype carriers from the SWOC group (p < 0.05), but there were no differences in the sputum samples. CONCLUSION: The rs13147758 GG genotype and the rs13147758-rs1828591 GA haplotype are associated with susceptibility to COPD. Furthermore, an association in protein levels was observed between the HHIP rs13147758 genotype and COPD in Mexican mestizo smokers.

The breadth of the Mexican Transition Zone as defined by its flowering plant generic flora.

Biogeographic regions are defined by taxa with similar distribution patterns. Flowering plants have been widely used to propose biogeographic regionalization schemes because of shared historical or ecological factors that determine their distribution. The Mexican Transition Zone represents the boundary between the Nearctic and Neotropical kingdoms; however, there is no general agreement about the limits and extent of this region. Despite the significance of its role in the history of Mexican biota, no study involving a set of relevant plant taxa validates the magnitude of the Mexican Transition Zone. This work attempts to determine the proportion of flowering plant families and genera that characterize the biogeographic kingdoms and the Mexican Transition Zone. Through identification of distinctive genera it is shown that the Mexican Transition Zone includes the mountains of Mexico, from Oaxaca northwards. The results provide a broad view of the distribution patterns of the flora of Mexico and allow the evaluation of relationships and floristic affinities.

Heterozygous Genotype rs17580 AT (PiS) in SERPINA1 is Associated with COPD Secondary to Biomass-Burning and Tobacco Smoking: A Case-Control and Populational Study.

Purpose: The protease inhibitor S (PiS) and Z (PiZ) variants have been stated as the only genetic cause of chronic obstructive pulmonary disease (COPD) in Caucasians. However, its frequency in admixed populations is low. We aimed to identify genetic susceptibility between PiS (rs17580) and PiZ (rs28929474) polymorphisms with COPD related to tobacco smoking and biomass-burning smoke as well as to determine its frequencies in Mestizo and Amerindian populations from Mexico. Patients and Methods: One thousand and eight hundred seventy-eight subjects were included in two comparisons of cases and controls, (1) smokers with and without COPD (COPD-S, n=399; SWOC, n=1106); (2) Biomass-burning smoke-exposed subjects with and without COPD (COPD-BS, n=98; BBES, n=275). In addition, 2354 Mexican subjects identified as Mestizos (n=1952) and Amerindian (n=402) were included. The population structure was evaluated using 59 informative ancestry markers. Results: The AT genotype of rs17580 is associated with COPD in both comparisons (COPD-S vs SWOC p<0.001, OR=2.16; COPD-BS vs BBES p<0.0001, OR=11.50). The population of the Mexico-North has a greater Caucasian contribution (54.7%) compared to the center (46.9%) and southeast (42.7%). Conclusion: The rs17580, AT genotype, is associated with COPD in Mexican-Mestizo smokers and exposed to biomass-burning smoke. The rs17580 AT is more frequent in the Mexican-Mestizo population of the North of the country, which has a high Caucasian component.

Single Nucleotide and Copy-Number Variants in IL4 and IL13 Are Not Associated with Asthma Susceptibility or Inflammatory Markers: A Case-Control Study in a Mexican-Mestizo Population.

BACKGROUND: Asthma is a complex and chronic inflammatory airway disease. Asthma's etiology is unknown; however, genetic and environmental factors could affect disease susceptibility. We designed a case-control study aimed to evaluate the role of single-nucleotide polymorphisms (SNP), and copy-number variants (CNV) in the IL4 and IL13 genes in asthma susceptibility and their participation in plasma cytokine levels depending on genotypes Methods: We include 486 subjects, divided into asthma patients (AP, n = 141) and clinically healthy subjects (CHS, n = 345). We genotyped three SNP, two in the IL4 and two in the IL13 gene; also, two CNVs in IL4. The IL-4, IL-13 and IgE plasma levels were quantified. RESULTS: Biomass-burning smoke exposure was higher in the AP group compared to CHS (47.5% vs. 20.9%; p < 0.01, OR = 3.4). No statistical differences were found in the genetic association analysis. In both CNV, we only found the common allele. For the analysis of IL-4, IL-13, and IgE measures stratified by genotypes, no significant association or correlation was found. CONCLUSION: In the Mexican-mestizo population, SNPs neither CNVs in IL4 nor IL13 are associated with asthma susceptibility or involved serum cytokine levels. Biomass-burning smoke is a risk factor in asthma susceptibility.