[Multilevel tuberculous spondylitis]. / Espondilitis tuberculosa multinivel.

A case of a 20-year-old man with multilevel non-contiguous tuberculous spondylitis (cervical, dorsal 6, dorsal 10 and lumbar) is presented. In the context of disseminated tuberculosis in an HIV-negative patient with serious compromise of his general condition and multiple locations of the disease, some of these with fistulas that secreted caseum. The acute paraplegia led, considering the sensory level at dorsal 6, to a first urgent decompression surgery via the posterior approach. A scheduled surgery was then performed, first in the cervical region via the anterior approach, with corpectomy, placement of a vertebral body replacement plus autologous graft and plate with screws. Subsequently, dislocation of dorsal level 6 was evidenced backwards, compressing the spinal cord and, given the mechanical instability, a third surgical stage was indicated by posterior approach, which included reduction, decompression and fixation, resolving the three levels by posterior approach with bars and screws. The surgical, medical and physiotherapy treatment of this rare form of Pott's disease was successful, with recovery of his mechanical stability and progressive recovery of his neurological status. The surgical, medical and physiotherapy treatment of this rare form of Pott's disease was successful, with recovery of his mechanical stability and progressive recovery of his neurological status.

Se presenta el caso de un varón de 20 años con espondilitis tuberculosa multinivel no contigua (cervical, dorsal 6, dorsal 10 y lumbar). Se trata de un paciente HIV negativo con tuberculosis diseminada con grave compromiso de su estado general y múltiples localizaciones de la enfermedad. Algunas tenían fistulas que secretaban caseum. El paciente presentó paraplejía aguda que requirió, teniendo en cuenta el nivel sensitivo a nivel dorsal 6, una primera cirugía urgente de descompresión por vía posterior. Luego se efectuó la cirugía programada. En primera instancia, la región cervical por vía anterior, con corporectomía, colocación de reemplazo de cuerpo vertebral más injerto autólogo y placa con tornillos. Posteriormente se evidenció luxación del nivel dorsal 6 hacia atrás comprimiendo la médula espinal y, dada la inestabilidad mecánica, se indicó un tercer tiempo quirúrgico por vía posterior que comprendió reducción, descompresión y fijación, resolviendo los tres niveles por vía posterior con barras y tornillos. El tratamiento quirúrgico, médico y kinésico de esta forma poco frecuente del mal de Pott fue exitoso, con recuperación de su estabilidad mecánica y progresiva recuperación de su estado neurológico.

Espondilitis tuberculosa multinivel / Multilevel tuberculous spondylitis

Resumen Se presenta el caso de un varón de 20 años con espondilitis tuberculosa multinivel no contigua (cervical, dorsal 6, dorsal 10 y lumbar). Se trata de un paciente HIV negativo con tuberculosis dise minada con grave compromiso de su estado general y múltiples localizaciones de la enfermedad. Algunas tenían fistulas que secretaban caseum. El paciente presentó paraplejía aguda que requirió, teniendo en cuenta el nivel sensitivo a nivel dorsal 6, una primera cirugía urgente de descompresión por vía posterior. Luego se efectuó la cirugía programada. En primera instancia, la región cervical por vía anterior, con corporectomía, colocación de reemplazo de cuerpo vertebral más injerto autólogo y placa con tornillos. Posteriormente se evidenció luxación del nivel dorsal 6 hacia atrás comprimiendo la médula espinal y, dada la inestabilidad mecánica, se indicó un tercer tiempo quirúrgico por vía posterior que comprendió reducción, descompresión y fijación, resolviendo los tres niveles por vía posterior con barras y tornillos. El tratamiento quirúrgico, médico y kinésico de esta forma poco frecuente del mal de Pott fue exitoso, con recuperación de su estabilidad mecánica y progresiva recuperación de su estado neurológico.

Abstract A case of a 20-year-old man with multilevel non-contiguous tuberculous spondylitis (cervical, dorsal 6, dorsal 10 and lumbar) is presented. In the context of disseminated tuberculosis in an HIV-negative patient with serious compromise of his general condition and multiple locations of the disease, some of these with fistulas that secreted caseum. The acute paraplegia led, considering the sensory level at dorsal 6, to a first urgent decompression surgery via the posterior approach. A scheduled surgery was then performed, first in the cervical region via the anterior approach, with corpectomy, placement of a vertebral body replace ment plus autologous graft and plate with screws. Subsequently, dislocation of dorsal level 6 was evidenced backwards, compressing the spinal cord and, given the mechanical instability, a third surgical stage was indi cated by posterior approach, which included reduction, decompression and fixation, resolving the three levels by posterior approach with bars and screws. The surgical, medical and physiotherapy treatment of this rare form of Pott's disease was successful, with recovery of his mechanical stability and progressive recovery of his neurological status. The surgical, medical and physiotherapy treatment of this rare form of Pott's disease was successful, with recovery of his mechanical stability and progressive recovery of his neurological status.

Effect of gene-gene and gene-environment interactions associated with antituberculosis drug-induced hepatotoxicity.

OBJECTIVES: This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires. PATIENTS AND METHODS: We investigated 364 TB patients who received anti-TB drugs. Physicians collected demographic and clinical data to identify environmental risk factors for ATDH development. Polymorphisms were detected using gene sequencing, PCR, and PCR-restriction fragment length polymorphisms. A binary logistic regression analysis was carried out to compare the results of TB patients with and without the development of hepatotoxicity. The multifactor dimensionality reduction method was used to examine genetic and environmental interactions in association with ATDH. RESULTS: This study suggests that the slow acetylator profile [odds ratio (OR): 3.02; 95% confidence interval (CI): 1.82-5.00; P<0.001], genotypes carrying the c2 variant (OR: 2.16; 95% CI: 1.33-3.51; P=0.002) or the A4 variant of CYP2E1 (OR: 2.13; 95% CI: 1.06-4.29; P=0.050), and female sex (OR: 1.94; 95% CI: 1.20-3.14; P=0.006) were independent predictor variables for ATDH. Patients carrying the slow acetylator profile and the c2 variant showed an increased risk (OR: 7.068; 95% CI: 3.34-14.95; P<0.001). We also identified a synergic interaction (epistasis) between GSTT1 and CYP2E1 associated with an increased risk for ATDH. A meaningful gene-environment interaction was associated with an increased risk of ATDH [testing balance accuracy=0.675 (P=0.001) and cross-validation consistency=10/10]. CONCLUSION: ATDH is a severe and prevalent adverse drug reaction and leads to drug discontinuation in 11% of TB patients. Our study created a prediction model that properly classified the 67.5% of TB patients in their risk of developing ATDH. The considerable number of TB patients in our country supports the use of pharmacogenetic testing and a comprehensive clinical history to identify patients with a high risk of suffering hepatotoxicity.

tagSNP rs1495741 as a useful molecular marker to predict antituberculosis drug-induced hepatotoxicity.

INTRODUCTION: It has been widely reported that the slow acetylator phenotype of N-acetyltransferase 2 (NAT2) is associated with the development of antituberculosis drug-induced hepatotoxicity (ATDH). The aim of this report was to evaluate the level of agreement and accuracy of two recently recommended markers, the two-single nucleotide polymorphisms (SNP) (C282T and T341C) and tagSNP of NAT2 (rs1495741) genotypes, to predict the seven-SNP-inferred NAT2 phenotype in Bolivian and Argentinian tuberculosis (TB)-patient populations. In addition, we analyzed the association of these markers with ATDH. METHODS: We examined 331 TB patients who had been treated with anti-TB drugs. TagSNP of NAT2 genotyping was determined using PCR-restriction fragment length polymorphisms. The seven SNPs of NAT2 were determined using sequencing. Concordance analysis was carried out using Kendall's tau-b coefficient (w) and the degree of agreement with Cohen's κ coefficient (κ). Receiver operating characteristic receiver operating characteristic curves were obtained to measure the specificity and sensitivity of the method. A binary logistic regression was performed to identify variables associated with the development of ATDH. RESULTS: Both predictors showed a remarkable concordance (>95.0%) and an almost perfect agreement (κ>0.945; P<0.0001) with the predicted acetylator profile. However, the sensitivity of the tagSNP genotypes to predict the NAT2 acetylator phenotype was lower in the Bolivian population (92.3%) compared with the Argentinian population (100.0%). CONCLUSION: A nearly perfect agreement between both predictors and the predicted acetylation profile was observed with very high levels of sensitivity (>97%) and specificity (>98.0%). Furthermore, and as expected, both the two-SNP (C282T, T341C) and tagSNP were found to be independent variables in predicting ATDH with the same strength as seven-SNP of NAT2.

Inusual presentación infecciosa oportunista en pulmón secuelar: reporte de un caso clínico / A Rare Opportunist Infectious Complication in a Lung with Sequelae; Report of a Clinical Case

El aspergiloma se considera la forma clínica más frecuente y mejor reconocida de la aspergilosis pulmonar, que surge como resultado de la colonización por el hongo de una cavidad, quiste o bulla ya existentes, como consecuencia de enfermedades crónicas tales como tuberculosis, bronquiectasias, enfisema bulloso, fibrosis pulmonar o sarcoidosis en estadios avanzados. La presentación de múltiples aspergilomas es infrecuente, lo más común es la presencia de una sola bola fúngica.

Aspergilloma is considered the most common and best known cause of pulmonary aspergillosis, which arises by the fungal colonization of a lung cavity, a cyst or existing bullae resulting from chronic diseases such as tuberculosis, bronchiectasis, bullous emphysema, pulmonary fibrosis and sarcoidosis in advanced stages. The presentation of multiple aspergillomas is infrequent. A single fungal ball-like mass is the most common presentation.

Sex, ethnicity, and slow acetylator profile are the major causes of hepatotoxicity induced by antituberculosis drugs.

BACKGROUND AND AIM: Treatment with antituberculosis (TB) drugs produces liver damage in a large proportion of patients. Isoniazid, an antibacterial drug, is primarily responsible for this hepatotoxicity. Several polymorphisms of the N-acetyltransferase 2 (NAT-2) and cytochrome P450 2E1 enzymes, which are involved in the metabolism of isoniazid, may be directly associated with the development of hepatotoxicity. This study was designed to analyze the association between the NAT-2 and CYP2E1 polymorphisms with the development of anti-TB drug-induced hepatotoxicity (ATDH). METHODS: One hundred and seventy-five TB patients who had been treated with anti-TB drugs were studied. The allelic and genotypic frequency distributions of the NAT-2 and CYP2E1 enzymes were studied using polymerase chain reaction-restriction fragment length polymorphisms methodology. A binary logistic regression analysis was used to compare the results between TB patients with and without the development of hepatotoxicity. RESULTS: Having a slow acetylator status (odds ratio [OR] = 2.615; confidence interval [CI] = 1.264-5.411; P = 0.01), being female (OR = 2.734; CI = 1.325-5.639, P = 0.006), and having Bolivian ethnicity (OR = 2.711; CI = 1.307-6.625, P = 0.007) were found to be independent predictor variables for ATDH. CONCLUSIONS: This study showed that a patient's NAT-2 acetylator status, gender, and ethnic origin may be regarded as important risk factors for developing hepatotoxicity. Contrary to expectations, the CYP2E1 c1/c2 polymorphism did not show a significant association with hepatotoxicity in this study. Given the increases in TB cases and ATDH incidence levels, as well as the associated hospitalization costs, it may also be helpful to know patients' acetylator status prior to or at the beginning of the TB treatment regimen.