Development and validation of a predictive model for choledocholithiasis.

BACKGROUND: Gallstone-related conditions affect a significant portion of the population, with varying prevalence among different ethnic groups. Complications such as pancreatitis and cholangitis are associated with the presence of common bile duct (CBD) stones. Existing guidelines for diagnosing choledocholithiasis lack precision, leading to excessive use of invasive procedures like endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A prospective study was conducted at Hospital Central "Dr. Ignacio Morones Prieto," involving 374 patients in the development cohort and 154 patients in the validation cohort. Patients meeting inclusion criteria underwent biochemical testing and ultrasonography. A predictive scoring system was developed using logistic regression and validated in an independent cohort. Clinical and laboratory variables were collected, and model performance was assessed using receiver-operator characteristic (ROC) curves. RESULTS: The predictive model incorporated variables such as age, pancreatitis, cholangitis, bilirubin levels, and CBD stone presence on ultrasound. The model demonstrated an area under the ROC curve (AUC) of 93.81% in the validation dataset. By adjusting the threshold defining high-risk probability to 40%, the model improved specificity and sensitivity compared to existing guidelines. Notably, the model reclassified patients, leading to a more accurate risk assessment. CONCLUSIONS: The developed algorithm accurately predicts choledocholithiasis non-invasively in patients with symptomatic gallstones. This tool has the potential to reduce reliance on costly or invasive procedures like magnetic resonance cholangiopancreatography and ERCP, offering a more efficient and cost-effective approach to patient management. The user-friendly calculator developed in this study could streamline diagnostic procedures, particularly in resource-limited healthcare settings, ultimately improving patient care.

Factors Associated With Mortality in Patients With Immune-Mediated Rheumatic Diseases and COVID-19 From Latin America: Data From Argentina, Mexico, and Brazil.

OBJECTIVE: To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population. METHODS: Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded. RESULTS: A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6-12.4), male sex (OR, 1.5; 95% CI, 1.1-2.1), living in Mexico (OR, 3.0; 95% CI, 2.0-4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0-2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3-2.4), and other diseases (OR, 2.6; 95% CI, 1.6-4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5-7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4-2.5) or rituximab (OR, 4.2; 95% CI, 2.7-6.6) were associated with mortality. CONCLUSIONS: Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results.

An Analysis COVID-19 in Mexico: a Prediction of Severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a mild illness in most cases; forecasting COVID-19-associated mortality and the demand for hospital beds and ventilators are crucial for rationing countries' resources. OBJECTIVE: To evaluate factors associated with the severity of COVID-19 in Mexico and to develop and validate a score to predict severity in patients with COVID-19 infection in Mexico. DESIGN: Retrospective cohort. PARTICIPANTS: We included 1,435,316 patients with COVID-19 included before the first vaccine application in Mexico; 725,289 (50.5%) were men; patient's mean age (standard deviation (SD)) was 43.9 (16.9) years; 21.7% of patients were considered severe COVID-19 because they were hospitalized, died or both. MAIN MEASURES: We assessed demographic variables, smoking status, pregnancy, and comorbidities. Backward selection of variables was used to derive and validate a model to predict the severity of COVID-19. KEY RESULTS: We developed a logistic regression model with 14 main variables, splines, and interactions that may predict the probability of COVID-19 severity (area under the curve for the validation cohort = 82.4%). CONCLUSIONS: We developed a new model able to predict the severity of COVID-19 in Mexican patients. This model could be helpful in epidemiology and medical decisions.

Population pharmacokinetics of mycophenolic acid in Mexican patients with lupus nephritis.

BACKGROUND: Mycophenolic acid (MPA) is an effective oral immunosuppressive drug used to treat lupus nephritis (LN), which exhibits large pharmacokinetic variability. This study aimed to characterize MPA pharmacokinetic behaviour in Mexican LN patients and to develop a population pharmacokinetic model which identified factors that influence MPA pharmacokinetic variability. METHODS: Blood samples from LN patients treated with mycophenolate mofetil (MMF) were collected pre dose and up to six hours post dose. MPA concentrations were determined by a validated ultra-performance liquid chromatography tandem mass spectrometry technique. Patients were genotyped for polymorphisms in enzymes (UGT1A8, 1A9 and 2B7) and transporters (ABCC2 and SLCO1B3). The anthropometric, clinical, genetic and co-medication characteristics of each patient were considered as potential covariates to explain the variability. RESULTS: A total of 294 MPA concentrations from 40 LN patients were included in the development of the model. The data were analysed using NONMEM software and were best described by a two-compartment linear model. MPA CL, Vc, Vp, Ka and Q were 15.4 L/h, 22.86 L, 768 L, 1.28 h-1 and 20.3 L/h, respectively. Creatinine clearance and prednisone co-administration proved to have influence on clearance, while body weight influenced Vc. The model was internally validated, proving to be stable. MMF dosing guidelines were obtained through stochastic simulations performed with the final model. CONCLUSIONS: This is the first MPA population pharmacokinetic model to have found that co-administration of prednisone results in a considerable increase on clearance. Therefore, this and the other covariates should be taken into account when prescribing MMF in order to optimize the immunosuppressant therapy in patients with LN.

Desempeño de las ecuaciones para estimar la tasa de filtración glomerular en pacientes mexicanos receptores de trasplante renal.

INTRODUCTION: The management of kidney transplant recipients requires glomerular filtration rate (GFR) monitoring, which is an indicator of graft primary function and patient survival. OBJECTIVE: To evaluate the performance of different creatinine or cystatin-based formulas in the estimation of glomerular filtration rate in Mexican patients receiving kidney transplantation. METHOD: 30 transplant recipients were included, in whom the glomerular filtration rate was measured by means of iothalamate, and was also calculated using seven equations based on cystatin or creatinine. RESULTS: The formula with the best performance was the one proposed by the chronic kidney disease epidemiology collaboration (CKD-EPI), with a bias of -2.4 mL/min/1.73 m2 and an accuracy of 9.6; 96.7 % of patients were within 30 % of the measured GFR. The second best formula was the modification of diet in renal disease (MDRD) equation. Cystatin-based equations showed a poor performance. CONCLUSIONS: Our study suggests that, in Mexican patients receiving kidney transplantations, the best equations to estimate GFR are the CKD-EPI and MDRD equations.

INTRODUCCIÓN: El manejo de los pacientes receptores de trasplante renal requiere vigilancia de la tasa de filtrado glomerular (TFG), la cual es un indicador de la función primaria del injerto y de la supervivencia del paciente. OBJETIVO: Evaluar el rendimiento en la estimación de la función renal de diferentes fórmulas basadas en creatinina o cistatina en pacientes mexicanos receptores de trasplante renal. MÉTODO: Se incluyeron 30 pacientes receptores de trasplante renal en quienes se midió tasa de filtrado glomerular por iodotalamato, la cual también se calculó por siete ecuaciones basadas en cistatina o creatinina. RESULTADOS: La fórmula con mejor desempeño fue la propuesta por CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), con un sesgo de −2.4 mL/minuto/1.73 m2 y precisión de 9.6; 96.7 % estaba dentro de 30 % de la tasa de filtrado glomerular medida. La segunda mejor ecuación fue la MDRD (Modification of Diet in Renal Disease). Las ecuaciones basadas en cistatina mostraron pobre desempeño. CONCLUSIONES: Nuestro estudio sugiere que en pacientes mexicanos receptores de trasplante renal las mejores ecuaciones para estimar la TFG son CKD y MDRD.

Diffuse Alveolar Hemorrhage in Autoimmune Diseases.

PURPOSE OF REVIEW: The present paper establishes a narrative and analytical review of diffuse alveolar hemorrhage (DAH) in ANCA-associated vasculitis, systemic lupus erythematosus, and antiphospholipid syndrome. RECENT FINDINGS: Recent studies found a frequent association between DAH and infections and systemic lupus erythematosus and its associated factors. Biological therapies like rituximab have demonstrated benefit mainly in patients with ANCA-associated vasculitis. Main clinical manifestations of diffuse alveolar hemorrhage in these three diseases include dyspnea, pulmonary infiltrates, cough, and hypoxemia. The presence of hemorrhagic bronchoalveolar lavage, hemosiderin containing macrophages, or an increase of carbon monoxide diffusing capacity have been described in some series as helpful findings for the diagnosis. Hemoptysis has been seen mainly in systemic lupus erythematosus. The cornerstone of therapy includes glucocorticoids and cyclophosphamide, and recent findings in ANCA-associated vasculitis suggest the similar benefit of rituximab. Future evaluations and systematic reviews will help to define the real benefit for therapies that appeared to be controversial at the moment.

Clinical outcomes and risk factors for posterior reversible encephalopathy syndrome in systemic lupus erythematosus: a multicentric case-control study.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a well-known but rare complication in patients (<1%) with systemic lupus erythematosus (SLE). However, current epidemiological data are quite scant. The aim of the present study was to describe potentially unrecognised risk factors. PATIENTS AND METHODS: We performed a multicentre, retrospective case-control study in Mexico between 1999 and 2014. We included a total of 168 patients who accounted for 77 episodes of PRES, as follows: SLE/PRES, 43 patients with 48 episodes; SLE without PRES, 96 patients; and PRES without SLE, 29 patients. SLE diagnosis was considered when patients fulfilled ≥4 American College of Rheumatology criteria. PRES was defined by reversible neurological manifestations and MRI changes. RESULTS: Patients with SLE/PRES were younger, presented with seizures as the most common manifestation (81%) and 18% had the typical occipital MRI finding. Hypertension (OR=16.3, 95% CI 4.03 to 65.8), renal dysfunction (OR=6.65, 95% CI 1.24 to 35.6), lymphopenia (OR=5.76, 95% CI 1.36 to 24.4), Systemic Lupus Erythematosus Activity Index ≥ 6 points (OR=1.11, 95% CI 1.01 to 1.22) and younger age (OR=0.86, 95% CI 0.81 to 0.91, p<0.001) were independent risk factors for development of PRES in SLE. Furthermore, dyslipidemia also characterised the association between PRES and SLE (OR=10.6, 95% CI 1.17 to 96.4). CONCLUSIONS: This is the largest reported series of patients with SLE and PRES. We were able to corroborate the known risk factors for of PRES, and found two previously undescribed factors (lymphopenia and dyslipidemia), which suggests that endothelial dysfunction is a key element in PRES pathogenesis in lupus patients.

Influence of feeding practices in the composition and functionality of infant gut microbiota and its relationship with health.

Establishing the infant's gut microbiota has long-term implications on health and immunity. Breastfeeding is recognized as the best practice of infant nutrition in comparison with formula feeding. We evaluated the effects of the primary feeding practices by analyzing the infant growth and the potential association with gut diseases. A cross-sectional and observational study was designed. This study included 55 mothers with infants, who were divided according to their feeding practices in breastfeeding (BF), formula feeding (FF), and combined breast and formula feeding (CF). Anthropometric measurements of the participants were recorded. Additionally, non-invasive fecal samples from the infants were collected to analyze the microbiota by sequencing, immunoglobulin A (IgA) concentration (ELISA), and volatile organic compounds (gas chromatography with an electronic nose). Results showed that the microbiota diversity in the BF group was the highest compared to the other two groups. The IgA levels in the BF group were twice as high as those in the FF group. Moreover, the child´s growth in the BF group showed the best infant development when the data were compared at birth to the recollection time, as noted by the correlation with a decreased concentration of toxic volatile organic compounds. Interestingly, the CF group showed a significant difference in health status when the data were compared with the FF group. We conclude that early health practices influence children's growth, which is relevant to further research about how those infants' health evolved.

Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People With Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry.

OBJECTIVE: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. METHODS: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. RESULTS: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. CONCLUSION: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

Renal function assessment in patients with systemic lupus erythematosus.

Few studies have evaluated the glomerular filtration rate (GFR) in patients with systemic lupus erythematosus (SLE). Even though the National Kidney Foundation (NKF) suggests using the equations to estimate GFR, rheumatologists continue using creatinine clearance (CCl). The main objective of our study was the assessment of different equations to estimate GFR in patients with SLE: Simplified MDRD study equation (sMDRD), CCl, Cockcroft Gault (CG), CG calculated with ideal weight (CGi), Mayo Clinic Quadratic (MCQ), and Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI). CKD-EPI was considered as the reference standard, and it was compared with the other equations to evaluate bias, correlation (r), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), percentage of measurement of GFR between 70-130% of GFR measured through CKD-EPI (P30) and to compute the ROC curves. Adequacy of the 24-h urine collection was evaluated. To classify patients into GFR < 60 ml/min/1.73 m(2), the best sensitivity and NVP were obtained with sMDRD: the best PPV and specificity with MCQ. P30 was 99.3% with sMDRD, 77.5% CCl, 91.7% CG, 96.7% CGi, and 77.2% with MCQ. The lowest bias was for sMDRD and the highest for CCl. Only 159 (52.6%) urine collections were considered adequate, and when these patients were re-evaluated, the statistical results improved for CCl. CGi was better in general than CG. CCl should not be considered as an adequate GFR estimation. Ideal weight is better than real weight to calculate GFR through CG in patients with SLE.

Disease activity and therapeutic drug monitoring of polyglutamates of methotrexate after daily or weekly administration of low-dose methotrexate in patients recently diagnosed with rheumatoid arthritis.

Low-dose methotrexate can be challenging to treat rheumatoid arthritis due to side effects, lack of adherence and risk of medication errors. The aim of this study was to explore the safety and efficacy of low-dose methotrexate administered daily or weekly in patients with rheumatoid arthritis. Patients were randomized according to a total oral dose of 12.5 mg of methotrexate administered: (A) divided in 5 days/week and (B) once per week. Patients were assessed along 24 weeks after starting treatment. Polyglutamates of methotrexate were quantified by ultrahigh-performance liquid chromatography coupled to tandem mass spectrometer. Patients from groups A and B showed a good response to methotrexate treatment in 29% and 25.5%, respectively, and a global frequency of adverse events of 37%. Methotrexate polyglutamate 3 concentrations were higher in normal weight (body mass index 18.5-24.9 kg/m2 ) than in obese (body mass index 30 kg/m2 ) patients with a median (interquartile range) of 28 (17.95-45.15) and 10.35 (5.22-30.88) nM without differences between dosage groups. Daily dosage regimen represents a therapeutic alternative without compromising the efficacy and safety of methotrexate treatment and with similar adherence patterns than weekly dosage regimen; further, methotrexate polyglutamate 3 concentrations could be a useful tool for therapeutic drug monitoring purposes.

SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry.

OBJECTIVE: While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2. METHODS: We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. RESULTS: SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. CONCLUSION: More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.

Surgical procedure versus medical treatment for infective endocarditis associated to mortality in Mexican population.

BACKGROUND: Early surgical procedures on patients with infective endocarditis (IE) have shown a clearly benefit to reduce embolization at the central nervous system. We conducted a retrospective cohort in Mexican population to evaluate mortality and clinical outcomes in patients with IE with or without surgical intervention. OBJECTIVES: Our aim was to evaluate factors associated with mortality in patients with IE and compare both groups with and without a surgical intervention. METHODS: We evaluated a retrospective cohort of patients who had been diagnosed with IE according to the Duke's criteria at our Institution in SLP, Mexico, from January 2001 to September 2016. We compared the risk factors associated to mortality of patients with or without surgery. Our primary outcome was mortality within 6 months of follow-up after the diagnosis. RESULTS: We included 105 patients, 51 (48.6%) were men, median age 46 [Q1 30, Q3 59] years, 36 patients (34.3%) received surgical treatment (STG), and 69 (65.7%) only medical treatment (MTG) group; 41 patients (39%) died during the study period; in the surgery group eight patients died (22%); and 33 in the MT group (47%) p = 0.049. Adjusted for APACHE II, surgery, creatinine levels and the size of vegetation, the surgery group had lower mortality than patients on MTG (HR 0.36, p = 0.047). CONCLUSION: As previously described in the literature, patients who underwent surgery had lower mortality than the patients who only received medical treatment; however, the Mexican population is different to other populations group, due to higher risk of diabetes mellitus (28%) versus (10%) in global risk of DM in the world and its complications and other chronic diseases as arterial systemic hypertension. Thus, surgical treatment must be elected as goal standard treatment in patient's whit IE and presence of vegetation.

Antecedentes: Los procedimientos quirúrgicos tempranos en pacientes con endocarditis infecciosa (EI) han mostrado un beneficio claro para reducir la embolización en el sistema nervioso central. Realizamos una cohorte retrospectiva en ­población mexicana para evaluar la mortalidad y los resultados clínicos en pacientes con EI con o sin intervención quirúrgica. Objetivos: Nuestro objetivo fue evaluar los factores asociados a la mortalidad en pacientes con endocarditis infecciosa y comparar ambos grupos con y sin intervención quirúrgica. Métodos: Evaluamos una cohorte retrospectiva de pacientes que habían sido diagnosticados de EI según los criterios de Duke en nuestra Institución en SLP, México, desde enero de 2001 a septiembre de 2016. Comparamos los factores de riesgo asociados a la mortalidad de pacientes con o sin cirugía. Nuestro resultado primario fue la mortalidad dentro de los 6 meses de seguimiento después del diagnóstico. Resultados: Se incluyeron 105 pacientes, 51 (48.6%) eran hombres, mediana de edad46 [Q1 30, Q3 59] años, 36 pacientes (34.3%) recibieron tratamiento quirúrgico (STG) y 69 (65.7%) solo grupo de tratamiento médico (MTG); 41 pacientes (39%) murieron durante el período de estudio; en el grupo de cirugía fallecieron 8 pacientes (22%) y en el grupo de MT (47%) 33 p = 0.049. Ajustado por APACHE II, cirugía, niveles de creatinina y tamaño de la vegetación, el grupo de cirugía tuvo menor mortalidad que los pacientes en MTG (HR 0.36, p = 0.047). Conclusión: Como se ha descrito anteriormente en la literatura, los pacientes que se sometieron a cirugía tuvieron menor mortalidad que los pacientes que solo recibieron tratamiento médico, sin embargo, la población mexicana es diferente a otros grupos poblacionales, debido a un mayor riesgo de diabetes mellitus (28%) vs (10%) en otros países y sus complicaciones y otras enfermedades crónicas como hipertensión arterial sistémica. Por tanto, el tratamiento quirúrgico debe ser elegido como principal método de tratamiento en pacientes con endocarditis infecciosa y presencia de vegetaciones.

Methotrexate Triglutamate as a Determinant of Clinical Response in Mexican Patients With Rheumatoid Arthritis: Pharmacokinetics and Dose Recommendation.

Methotrexate is the gold standard treatment in rheumatoid arthritis. Once absorbed, it is internalized in cells, where glutamate residues are added to produce polyglutamated forms, which are responsible for the effect of methotrexate. The aim of the current study is to determine the relationship between methotrexate triglutamate concentrations and the clinical evolution in rheumatoid arthritis patients, as well as to characterize the variability in both features to propose strategies for low-dose methotrexate optimization. The quantification of methotrexate triglutamate concentration in red blood cells was performed through ultra-performance liquid chromatography coupled with mass spectrometry. Polymorphisms of genes involved in the formation of polyglutamates were determined by real-time polymerase chain reaction. A multivariate regression was performed to determine the covariates involved in the variability of methotrexate triglutamate concentrations and a population pharmacokinetics model was developed through nonlinear mixed-effects modeling. Disease activity score changed according to methotrexate triglutamate concentrations; patients with good response to treatment had higher concentrations than moderate or nonresponding patients. The methotrexate triglutamate concentrations were related to time under treatment, dose, red blood cells, and body mass index. A 1-compartment open model was selected to estimate the pharmacokinetic parameters; the typical total clearance (L/day) was determined as 1.45 * (body mass index/28 kg/m2 ) * (red blood cells/4.6 × 106 cells/µL) and the volume of distribution was 52.4 L, with an absorption rate of 0.0346/day and a fraction metabolized of 1.03%. Through the application of the model, the initial dose of methotrexate is proposed on the basis of stochastic simulations and considering methotrexate triglutamate concentrations found in responders patients.

Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment of Rheumatoid Arthritis, 2018. / Actualización de las guías del tratamiento farmacológico de la artritis reumatoide del Colegio Mexicano de Reumatología 2018.

Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. OBJECTIVE: To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. METHOD: Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. RESULTS: Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. CONCLUSIONS: The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.

Effects of Agave Fructans, Inulin, and Starch on Metabolic Syndrome Aspects in Healthy Wistar Rats.

Healthy Wistar rats were supplemented during 20 weeks with commercial inulin (I) and Agave tequilana fructans (CAT), experimental fructans from A. tequilana (EAT) and A. salmiana (AS) mature stems, rice starch 10% (RS), and standard feed for rodents (C). Feed intake was kept steady, but with I, body weight and abdominal adipose tissue (6.01 g) decreased at the end. Glucose (mg/dL) (C, 120.52; I, 110.69; CAT, 105.75; EAT, 115.48; AS, 101.63; and RS, 121.82), total cholesterol (C, 89.89; I, 64.48; CAT, 68.04; EAT, 68.74; AS, 68.04; and RS, 82), and triglycerides (C, 84.03; I, 59.52; CAT, 68.56; EAT, 59.08; AS, 75.27; and RS, 81.8) kept being normal and without differences between fructans. At the end, there was a significant increase in lactic acid bacteria when the I and AS groups were compared to the C group (C, 9.18; I, 10.64; CAT, 10.34; EAT, 10.36; AS, 10.49; and RS, 9.62 log 10 CFU/g of feces). In addition, with fructans, there was an accelerated process in feces emptiness, Lieberkühn crypts kept their morphology, and there was an increment of goblet cells.

Determination of Salivary Sialic Acid Through Nanotechnology: A Useful Biomarker for the Screening of Breast Cancer.

PURPOSE: To demonstrate the usefulness of sialic acid (SA) in saliva as a biomarker for breast cancer (BC) and develop a new tool for early detection. METHODS: Considering that the amount of SA in human saliva is limited, the levels of SA were measured using surface-enhanced Raman spectroscopy (SERS) with tailored citrate-reduced silver nanoparticles. We calibrated the spectrum using analytical reagent SA. The 164 patients included in this study were undergoing screening mammography and/or ultrasound testing. The SA test was performed in the absence of previous information regarding the health of the subjects. Biopsies were performed to determine the diagnosis of cancer condition. The biopsy studies determined that 35 patients are BC affected and 129 gave negative results. RESULTS: SERS showed a sensitivity and specificity of 80 and 93%, respectively. The cut-off value for SA (12.5 mg/dL) was established through a receiver operating characteristic (ROC) curve analysis. The area under the curve of the ROC analysis resulted in 95% with this SA level cut-off. Our results suggest that SA may be a useful biomarker for the screening of breast cancer in women. CONCLUSIONS: Our results suggest that the SA levels measured from saliva may be highly sensitive and specific markers for the presence of breast cancer.