Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

Tween 80 Improves the Acid-Fast Bacilli Quantification in the Magnetic Nanoparticle-Based Colorimetric Biosensing Assay (NCBA).

Despite its reduced sensitivity, sputum smear microscopy (SSM) remains the main diagnostic test for detecting tuberculosis in many parts of the world. A new diagnostic technique, the magnetic nanoparticle-based colorimetric biosensing assay (NCBA) was optimized by evaluating different concentrations of glycan-functionalized magnetic nanoparticles (GMNP) and Tween 80 to improve the acid-fast bacilli (AFB) count. Comparative analysis was performed on 225 sputum smears: 30 with SSM, 107 with NCBA at different GMNP concentrations, and 88 with NCBA-Tween 80 at various concentrations and incubation times. AFB quantification was performed by adding the total number of AFB in all fields per smear and classified according to standard guidelines (scanty, 1+, 2+ and 3+). Smears by NCBA with low GMNP concentrations (≤1.5 mg/mL) showed higher AFB quantification compared to SSM. Cell enrichment of sputum samples by combining NCBA-GMNP, incubated with Tween 80 (5%) for three minutes, improved capture efficiency and increased AFB detection up to 445% over SSM. NCBA with Tween 80 offers the opportunity to improve TB diagnostics, mainly in paucibacillary cases. As this method provides biosafety with a simple and inexpensive methodology that obtains results in a short time, it might be considered as a point-of-care TB diagnostic method in regions where resources are limited.

Disparities in cystic fibrosis survival in Mexico: Impact of socioeconomic status.

BACKGROUND: Median survival age in cystic fibrosis (CF) has increased in developed countries. Scarce literature exists about survival in Latin America, especially in Mexico. The aim of our study was to assess the median age of survival in CF patients and the impact of risk factors in Mexico over a 20-year period. METHODS: We conducted a retrospective study with all patients registered and followed in the CF Center in Monterrey, Mexico from 2000 to 2020. Median survival age was the primary outcome, assessed with Kaplan-Meier analysis. The influence of clinical, biological, and demographic factors on survival was analyzed with Cox regression model. RESULTS: Two-hundred five patients were included. Median survival for the cohort was 21.37 years (95% confidence interval [CI], 17.20-25.55). In the multivariate Cox regression model, low socioeconomic status (hazard ratio [HR], 4.21; 95% CI, 2.43-7.27), chronic Pseudomonas aeruginosa infection at 6 years (HR, 10.45; 95% CI, 5.66-19.28), and pancreatic insufficiency (HR, 3.13; 1.38-7.13) were independent risk factors for mortality. CONCLUSION: Median survival in Mexican patients with CF is lower than in high-income countries, and socioeconomic status plays a conspicuous role in the disparity. To increase patient survival for those residing in low-middle income countries, public health authorities must design policies that fully cover diagnosis and treatment strategies for the CF population.

Invaginación íleo-colónica en un paciente adolescente con fibrosis quística / Ileocolonic intussusception in an adolescent patient with cystic fibrosis

La invaginación intestinal ocurre cuando un segmento proximal de intestino se repliega dentro de la luz de un segmento distal adyacente y provoca obstrucción intestinal. Es una causa común de abdomen agudo en los dos primeros años de la vida, pero raro en niños mayores. Un varón de 16 años, con diagnóstico de fibrosis quística, se presentó con un cuadro compatible con síndrome de oclusión intestinal distal. Consultó a la clínica con dolor abdominal y una masa palpable en el hipocondrio derecho. Se realizó ecografía abdominal y tomografía de abdomen contrastada, que demostraron invaginación íleo-colónica con signos de isquemia intestinal, necrosis y neumatosis de la pared intestinal. Fue intervenido: se realizó resección del íleon terminal y hemicolon derecho, y se detectó una tumoración en ciego. La invaginación íleo-colónica es una causa rara de abdomen agudo en pacientes adolescentes con fibrosis quística y puede estar asociada a una causa orgánica subyacente.

Intestinal intussusception occurs when a proximal segment of the intestine telescopes into the lumen of an adjacent distal segment, causing intestinal obstruction. It is a common cause of acute abdomen in the first two years of life, but rare in older children. A 16-year-old male with a diagnosis of cystic fibrosis presented with symptoms compatible with distal intestinal occlusion syndrome. He came at the cystic fibrosis clinic with a 5-day evolution of abdominal pain and a palpable mass in the right hypochondrium. Abdominal ultrasound and abdominal contrasted tomography were performed demonstrating ileo-colonic invagination with signs of intestinal ischemia, necrosis and pneumatosis of the intestinal wall. He underwent surgery with resection of the terminal ileum and right hemicolon, ana tumor in the caecum was found. This is a rare cause of acute abdomen in young patients with cystic fibrosis and may be associated with an underlying organic cause.

[Ileocolonic intussusception in an adolescent patient with cystic fibrosis]. / Invaginación íleo-colónica en un paciente adolescente con fibrosis quística.

Intestinal intussusception occurs when a proximal segment of the intestine telescopes into the lumen of an adjacent distal segment, causing intestinal obstruction. It is a common cause of acute abdomen in the first two years of life, but rare in older children. A 16-year-old male with a diagnosis of cystic fibrosis presented with symptoms compatible with distal intestinal occlusion syndrome. He came at the cystic fibrosis clinic with a 5-day evolution of abdominal pain and a palpable mass in the right hypochondrium. Abdominal ultrasound and abdominal contrasted tomography were performed demonstrating ileocolonic invagination with signs of intestinal ischemia, necrosis and pneumatosis of the intestinal wall. He underwent surgery with resection of the terminal ileum and right hemicolon, and a tumor in the caecum was found. This is a rare cause of acute abdomen in young patients with cystic fibrosis and may be associated with an underlying organic cause.

La invaginación intestinal ocurre cuando un segmento proximal de intestino se repliega dentro de la luz de un segmento distal adyacente y provoca obstrucción intestinal. Es una causa común de abdomen agudo en los dos primeros años de la vida, pero raro en niños mayores. Un varón de 16 años, con diagnóstico de fibrosis quística, se presentó con un cuadro compatible con síndrome de oclusión intestinal distal. Consultó a la clínica con dolor abdominal y una masa palpable en el hipocondrio derecho. Se realizó ecografía abdominal y tomografía de abdomen contrastada, que demostraron invaginación íleo-colónica con signos de isquemia intestinal, necrosis y neumatosis de la pared intestinal. Fue intervenido: se realizó resección del íleon terminal y hemicolon derecho, y se detectó una tumoración en ciego. La invaginación íleo-colónica es una causa rara de abdomen agudo en pacientes adolescentes con fibrosis quística y puede estar asociada a una causa orgánica subyacente.

Magnetic Nanoparticle-Based Biosensing Assay Quantitatively Enhances Acid-Fast Bacilli Count in Paucibacillary Pulmonary Tuberculosis.

A new method using a magnetic nanoparticle-based colorimetric biosensing assay (NCBA) was compared with sputum smear microscopy (SSM) for the detection of pulmonary tuberculosis (PTB) in sputum samples. Studies were made to compare the NCBA against SSM using sputum samples collected from PTB patients prior to receiving treatment. Experiments were also conducted to determine the appropriate concentration of glycan-functionalized magnetic nanoparticles (GMNP) used in the NCBA and to evaluate the optimal digestion/decontamination solution to increase the extraction, concentration and detection of acid-fast bacilli (AFB). The optimized NCBA consisted of a 1:1 mixture of 0.4% NaOH and 4% N-acetyl-L-cysteine (NALC) to homogenize the sputum sample. Additionally, 10 mg/mL of GMNP was added to isolate and concentrate the AFB. All TB positive sputum samples were identified with an increased AFB count of 47% compared to SSM, demonstrating GMNP's ability to extract and concentrate AFB. Results showed that NCBA increased AFB count compared to SSM, improving the grade from "1+" (in SSM) to "2+". Extending the finding to paucibacillary cases, there is the likelihood of a "scant" grade to become "1+". The assay uses a simple magnet and only costs $0.10/test. NCBA has great potential application in TB control programs.

A High Level of Soluble CD40L Is Associated with P. aeruginosa Infection in Patients with Cystic Fibrosis.

OBJECTIVE: The aim of this study was to evaluate whether the concentration of sCD40L, a product of platelet activation, correlates with the presence of Pseudomonas aeruginosa in the airway of patients with cystic fibrosis (CF) and to determine its possible clinical association. METHODS: Sixty patients with CF, ranging in age from 2 months to 36 years, were studied. The demographics, cystic fibrosis transmembrane conductance regulator (CFTR) genotype, spirometry measurements, radiographic and tomographic scans, platelet count in peripheral blood, sCD40L, IL-6, TNF-α and ICAM1 data were collected. Infection-colonization of the airway was evaluated using sputum and throat swab cultures; the levels of anti-Pseudomonas aeruginosa antibodies (Anti-PaAb) were evaluated. RESULTS: Patients with CF and chronic colonization had anti-PaAb values of 11.6 ± 2.1 ELISA units (EU) and sCD40L in plasma of 1530.9 ±1162.3 pg/mL; those with intermittent infection had 5.7 ± 2.7 EU and 2243.6 ± 1475.9 pg/mL; and those who were never infected had 3.46 ± 1.8 EU (p≤0.001) and 1008.1 ± 746.8 pg/mL (p≤0.01), respectively. The cutoff value of sCD40L of 1255 pg/mL was associated with an area under the ROC (receiver operating characteristic curve) of 0.84 (95% CI, 0.71 to 0.97), reflecting P. aeruginosa infection with a sensitivity of 73% and a specificity of 89%. Lung damage was determined using the Brasfield Score, the Bhalla Score, and spirometry (FVC%, FEV1%) and found to be significantly different among the groups (p≤0.001). CONCLUSION: Circulating sCD40L levels are increased in patients with cystic fibrosis and P. aeruginosa infection. Soluble CD40L appears to reflect infection and provides a tool for monitoring the evolution of lung deterioration.

The +1858 C/T Polymorphism in the PTPN22 Gene Is Associated with Cystic Fibrosis Patients in Northeast Mexico.

Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population, but it has also been widely diagnosed in the Mexican population. Production of viscous secretions affects the secretory epithelia and the respiratory condition usually leads to death. The relationship between the CFTR genotype and the disease phenotype is not well understood. Other risk factors such as genetic and autoimmune influence the development of this disease. We analyzed the PTPN22 R620W polymorphism (+1858 C/T, rs2476601) in 78 DNA samples from CF patients and 232 healthy controls from northeast Mexico using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method. The C allele and the CC genotype were the most frequently detected in controls (CC genotype 96.12%; C allele 98.06%) compared with CF patients (CC genotype 88.46%, C allele 93.59%). A statistically significant association for the CT + TT genotypes (p = 0.012, OR = 3.232) as well as for the mutant T allele (p = 0.005, OR = 3.463) was found when comparing CF patients with controls. A significant association was found between the rs2476601 polymorphism of the PTPN22 gene and CF in Mexican patients. Further studies are necessary to understand the influence of this variant on lung neutrophil function and disease development.

Human multidrug-resistant Mycobacterium bovis infection in Mexico.

Here, we describe the molecular characterization of six human Mycobacterium bovis clinical isolates, including three multidrug resistant (MDR) strains, collected in Mexico through the National Survey on Tuberculosis Drug Resistance (ENTB-2008), a nationally representative survey conducted during 2008-2009 in nine states with a stratified cluster sampling design. The genetic background of bovine M. bovis strains identified in three different states of Mexico was studied in parallel to assess molecular relatedness of bovine and human strains. Additionally, resistance to first and second line anti-tuberculosis (TB) drugs and molecular identification of mutations conferring drug resistance was also performed. All strains were characterized by spoligotyping and 24-loci MIRU-VNTRs, and analyzed using the SITVIT2 (n = 112,000 strains) and SITVITBovis (n = 25,000 strains) proprietary databases of Institut Pasteur de la Guadeloupe. Furthermore, data from this study (n = 55 isolates), were also compared with genotypes recorded for M. bovis from USA (n = 203), Argentina (n = 726), as well as other isolates from Mexico (independent from the present study; n = 147), to determine any evidence for genetic relatedness between circulating M. bovis strains. The results showed that all human M. bovis cases were not genetically related between them or to any bovine strain. Interestingly, a high degree of genetic variability was observed among bovine strains. Several autochthonous and presumably imported strains were identified. The emergence of drug-resistant M. bovis is an important public health problem that jeopardizes the success of TB control programs in the region.

Low-income status is an important risk factor in North East Mexican patients with cystic fibrosis.

BACKGROUND. Factors such as environment, income status, as well as access to proper healthcare influence the survival and quality of life of people affected by chronic diseases including cystic fibrosis (CF). Survival factors in Mexican patients with CF have not been reported before, even when it has been estimated that this disease could not be negligible in the Mexican population. OBJECTIVE. To compare the influence of the mutant allele ΔF508 and environmental factors on the survival of Mexican CF patients. MATERIAL AND METHODS. We collected epidemiological data of 40 patients molecularly tested between 1987 and 2008 in the Clínica de Fibrosis Quística from the Hospital Universitario of the Universidad Autónoma de Nuevo León in Northeastern México. Kaplan-Meier plots and survival statistics were estimated and compared. RESULTS. Survival analysis revealed statistical significance for low-income status (p = 3.13 x 10-6), cor pulmonale (p = 0.00169), severe pulmonary disease (p = 0.00136), and BMI ≤15 kg/m2 (p = 0.00678). Statistical significance was not observed for the predominant allele ΔF508 considering two (p = 0.992), one (p = 0.503) or no (p = 0.403) mutant allele. CONCLUSIONS. Low income status was the most detrimental factor; followed by cor pulmonale, severe pulmonary disease and BMI ≤ 15 kg/m2 for the survival in North East Mexican patients with CF. Carrying the ΔF508 allele did not influence survival.

The tumor necrosis factor α (-308 A/G) polymorphism is associated with cystic fibrosis in Mexican patients.

UNLABELLED: Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (-251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP. RESULTS: The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25-9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease. CONCLUSION: An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients.

[Impact of eradication of Pseudomonas aeruginosa on survival in Mexican patients with cystic fibrosis]. / Impacto de la erradicación de Pseudomonas aeruginosa sobre la sobrevida en pacientes con fibrosis quística del noreste de México.

INTRODUCTION: Patients with cystic fibrosis (CF) present lower airway infection with Pseudomonas aeruginosa. Treatment of initial infection is fundamental to reduce subsequent damage. MATERIAL AND METHODS: We evaluated the efficacy of eradication treatment of P. aeruginosa in patients with CF from northeast Mexico using two protocols: inhaled colistin/oral ciprofloxacin and nebulized tobramycin 300 mg/oral ciprofloxacin. The intervention group included 17 patients with CF and recent infection with P. aeruginosa. The control group consisted of 23 chronically colonized patients of comparable age. RESULTS: Patients received 27 courses of eradication treatment. P. aeruginosa was eradicated in 21/27 (77.77%). The infection free period was 16.9, 11.7 months (colistin) and 17 ± 9.7 months (tobramycin) with no statistically significant difference (P = 0.97). CONCLUSIONS: Treated patients maintained normal lung function, better nutritional status, and a better chest X-ray score. In the control group 17/23 (73.9%) patients died with no deaths in the study group.