Sergio Ponce-de-León

The Changing Clinical Spectrum of Human Immunodeficiency Virus (HIV)-Related Oral Lesions in 1,000 Consecutive Patients: A 12-Year Study in a Referral Center in Mexico.

In developing countries, the variations in the clinical spectrum of human immunodeficiency virus (HIV)-related oral lesions over time, and the possible effects of antiretroviral therapy, have not been described. In this study we evaluate the clinical spectrum of oral lesions in a series of HIV-infected patients when first examined at the acquired immunodeficiency syndrome (AIDS) clinic of a tertiary care institution in Mexico City, Mexico, and the changes observed over 12 years.All HIV-infected adult patients had an oral examination performed by specialists in oral pathology and medicine who used established clinical diagnostic criteria for oral lesions. Four periods were defined according to the evolving pattern of antiretroviral use: the first 2 were before the introduction of highly active antiretroviral therapy (HAART) and the last 2 were during more established use of HAART.For the statistical analysis the chi-square test for contingency tables and the chi-square test for trend were utilized. For dimensional variables, except age, the Kruskal-Wallis or Mann-Whitney rank sum tests were used when applicable and trend was tested with the Spearman correlation coefficient. Age was tested through analysis of variance (ANOVA) and linear regression analysis. Alpha value was set at p = 0.05 for each test.In the 12-year study, 1,000 HIV-infected patients were included (87.9% male). At the baseline examination, oral lesions strongly associated with HIV were present in 47.1% of HIV-infected patients. Oral candidosis (31.6%), hairy leukoplakia (22.6%), erythematous candidosis (21.0%), and pseudomembranous candidosis (15.8%) were the most frequent lesions. Oral Kaposi sarcoma (2.3%), HIV-associated periodontal disease (1.7%), and oral non-Hodgkin lymphoma (0.1%) were less frequent.HIV-related oral lesions decreased systematically—by half during the course of the 4 study periods (p < 0.001). Except for Kaposi sarcoma, all oral lesions strongly associated with HIV showed a trend to decrease significantly during the study period. No apparent variation in the occurrence of salivary gland disease or human papillomavirus-associated oral lesions was found.A significant trend to a lower prevalence was observed in the group of patients who were already taking antiretroviral therapy, non-HAART and HAART (p < 0.001 and p = 0.004, respectively). Only a discrete reduction, barely significant, was noted among untreated patients (p = 0.060). By Period IV (1999–2001), those who received HAART showed the lowest prevalence of oral lesions strongly associated with HIV (p < 0.001).Patients with oral lesions strongly associated with HIV had significantly lower median CD4+ counts and higher viral loads than those without oral lesions strongly associated with HIV (p < 0.001 and p = 0.005, respectively). When CD4+ counts were correlated with prevalence of oral candidosis, a consistently negative association was found; this association prevailed even after the study group was partitioned according to period. In this selected cohort of 1,000 patients with HIV infection, the clinical spectrum of HIV-related oral lesions has changed over the 12-year study, with a decreased prevalence of most oral lesions. Our findings probably represent improvements in medical care of HIV-infected persons, earlier detection of HIV-infected patients at the AIDS clinic, the increasing use of prophylactic drugs to prevent secondary AIDS-related opportunistic infections, and, perhaps most important, the availability of potent antiretroviral therapy in recent years, since the introduction of HAART.

Oral Lesions as Clinical Markers of Highly Active Antiretroviral Therapy Failure: A Nested Case-Control Study in Mexico City

BACKGROUND Clinical markers that may predict virological failure during highly active antiretroviral therapy (HAART) have not been evaluated adequately. The aim of the present study was to evaluate the usefulness of human immunodeficiency virus (HIV)-related oral lesions as clinical predictors of virological failure in HIV-infected patients receiving HAART. METHODS A nested case-control study was conducted within a cohort of 1134 HIV-infected patients receiving HAART who attended the AIDS Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City during the period 1997-2005. Case patients were patients who, after achieving an undetectable viral load, had at least 1 viral load determination > or = 2000 copies/mL while receiving treatment. Control subjects were patients who, after achieving an undetectable viral load, continued to have undetectable viral loads during the follow-up period. There were 2-3 control subjects for each case patient, matched according to duration of follow-up. Oral examinations were blinded to viral loads and CD4+ lymphocyte counts. Analyses were performed with multivariate conditional logistic regression models, and associations were shown as odds ratios (ORs) with 95% confidence intervals (CI). Positive predictive values were calculated. RESULTS The target cohort consisted of 431 HIV-infected individuals; 47 case patients and 132 control subjects underwent complete oral examinations and formed the basis of the analysis. At the visit at which an undetectable viral load was determined, case patients and control subjects showed a similar frequency of HIV-related oral lesions (21.3% vs. 17.4%) (OR, 1.39; 95% CI, 0.57-3.38; P=.47). At the visit at which virological failure was determined, case patients showed a higher risk for HIV-related oral lesions (OR, 14.5; 95% CI, 4.21-49.94; P<.001) and oral candidosis (OR, 26.2; 95% CI, 3.34-205.9; P<.001) than did control subjects. The positive predictive value of HIV-related oral lesions and oral candidosis to identify patients who experienced virological failure while receiving HAART was 80% and 83%, respectively. CONCLUSIONS HIV-related oral lesions and, specifically, oral candidosis may be considered to be clinical markers of virological failure in HIV-infected patients receiving HAART.

Nutritional status and socio‐economic conditions as prognostic factors in the outcome of therapy in childhood acute lymphoblastic leukemia

The majority of children on earth are to be found in the developing world, many of them malnourished members of impoverished families. Thus, the effects of socio‐economic status (SES) on the therapeutic response of children with cancer are obviously relevant. The outcome of treatment in patients with the commonest form of cancer in childhood (acute lymphoblastic leukemia, ALL) is clearly related to their SES. Studies conducted mainly in developing countries have shown malnutrition to be an important prognostic factor in such children. However, other socio‐economic conditions could affect the outcome of therapy in patients with ALL: access to communications, transportation, laboratory studies and therapy. Even in children with an “adequate” SES, malnutrition is still an adverse prognostic factor. Nutritional supplementation appears to be a valuable addition to chemotherapy in undernourished children with ALL. The choice of treatment for these children should accomodate the cultural, economic and nutritional status of the patients and their families. Protocols must be created for testing methods of nutritional intervention and their influence on pharmacology, drug tolerance and survival in ALL. The influences of poverty and illiteracy on compliance with treatment, especially oral medication, need to be evaluated. Such investigations are essential to improve results of treatment of socio‐economically disadvantaged children suffering from ALL and other forms of cancer. Int. J. Cancer Supplement 11:52–55, 1998

Thalidomide as Therapy for Human Immunodeficiency Virus—Related Oral Ulcers: A Double-Blind Placebo-Controlled Clinical Trial

A double-blind, randomized, placebo-controlled clinical trial was performed in Mexico City to evaluate the efficacy of thalidomide in treating oral recurrent aphthae in human immunodeficiency virus (HIV)-infected subjects. Sixteen HIV-infected patients with clinical and histological diagnosis of oral recurrent aphthous ulcerations received randomly an 8-week course of either thalidomide or placebo, with an initial oral dosage of 400 mg/d for 1 week, followed by 200 mg/d for 7 weeks. Ten subjects received thalidomide and six received placebo. At 8 weeks, nine subjects (90%) in the thalidomide group had complete healing of their ulcers, compared with two (33.3%) of the six patients in the placebo group (P = .03). There was a significant reduction in largest ulcer diameter in the thalidomide group. Rash was observed in 80% of the thalidomide patients. Although thalidomide demonstrated an unquestionable benefit in treatment of oral ulcers in HIV patients, caution must be taken given the frequent occurrence of side effects.

Studies on lymphomata. III. Lymphomata, granulomata and tuberculosis

The presence of isolated epithelioid granulomata (EG) in the tissue samples of patients with malignant lymphomata (MT) has been related to a better prognosis. Miliary tuberculosis (MT) is frequent in Mexico (2.1 per 1000 patients at the Instituto Nacional de la Nutrición), where physicians dealing with the diagnostic and therapeutic approach of patients with ML and EG face the problem of differentiating the latter due to concurrent MT or to the neoplasm. Twenty‐five patients with ML + MT and seven with ML + EG without MT were identified along 12 years; 32 ML patients matched according to age, sex, stage, type of ML and treatment were selected and their survival compared with that of the former groups. The prevalence of MT in ML patients was 35 times higher than that of the general population (P < 0.001). Even though 6 and 18 month survival in patients with ML and MT or EG was higher than that of ML alone, differences are insignificant. It is concluded that the coexistence of MT and ML does not worsen the prognosis of ML; the high prevalence of MT in ML patients in selected countries could lead to the routinary administration of prophilactic antituberculous treatment. Cancer 52:258‐262, 1983.

Oral clinical markers and viral load in a prospective cohort of Mexican HIV-infected patients.

Recent cross-sectional studies have suggested that oral candidosis (OC) and hairy leukoplakia (HL) could be considered as clinical markers of high viral load levels and CD4 cell depletion in HIV infection [1-3]. However this association has not been documented in a prospective longitudinal study. Hence a cohort study was conducted to determine the association of the occurrence of OC and HL with HIV-ribonucleic acid plasma levels and CD4 T cell counts in Mexican HIV-infected individuals. Patients were examined for clinical evidences of current OC or HL at baseline and monthly during follow-up. Results revealed that the development of OC and HL in HIV-infected individuals with no treatment or under non-highly active antiretroviral therapy combinations appeared to be associated with the viral load values and lower CD4 cell counts. In conclusion the presence of these lesions may be considered to be good clinical indirect markers of the status of viral replication.

Bloodborne viral infections in patients attending an emergency room in Mexico City: estimate of seroconversion probability in healthcare workers after an occupational exposure.

The frequency of hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) I/II was determined in the emergency room of a teaching hospital. Of 909 patients, 19% had at least one infection; 7.8% had HCV, 6.9% HBV, 3.3% HIV, and 2.8% HTLV I/II. The probability that a healthcare worker would have an accident with an infected patient and seroconvert was 4.99 to 24.9 per 100,000 venipunctures for HBV, 5.6 to 8.4 for HCV, and 0.12-0.16 for HIV in our emergency room.

Impact of ertapenem on antimicrobial resistance in a sentinel group of Gram-negative bacilli: a 6 year antimicrobial resistance surveillance study

OBJECTIVES To determine the association between ertapenem and resistance of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii-calcoaceticus complex to different antimicrobials while adjusting for relevant hospital factors. METHODS This was a retrospective time-series study conducted at a tertiary care centre from September 2002 to August 2008. The specific impact of ertapenem on the resistance of these Gram-negative bacilli (GNB) was assessed by multiple linear regression analysis, adjusting for the average length of stay, rate of hospital-acquired infections and use of 10 other antimicrobials, including type 2 carbapenems. RESULTS Unadjusted analyses revealed significant increases over the duration of the study in the number of GNB resistant to meropenem/imipenem among 1000 isolates each of E. coli (0.46 ± 0.22, P < 0.05), P. aeruginosa (6.26 ± 2.26, P < 0.05), K. pneumoniae (8.06 ± 1.50, P < 0.0005) and A. baumannii-calcoaceticus complex (25.39 ± 6.81, P < 0.0005). Increased resistance to cefepime (and other extended-spectrum cephalosporins) was observed in E. coli (9.55 ± 1.45, P < 0.0005) and K. pneumoniae (15.21 ± 2.42, P < 0.0005). A. baumannii-calcoaceticus complex showed increased resistance to all antimicrobials except amikacin. After controlling for confounders, ertapenem was not significantly associated (P > 0.05) with changes in resistance for any pathogen/antimicrobial combination. CONCLUSIONS After controlling for confounders, ertapenem was not associated with changes in resistance in a group of sentinel GNB, although significant variations in resistance to different antimicrobials were observed in the unadjusted analyses. These results emphasize the importance of implementation of local resistance surveillance platforms and stewardship programmes to combat the global emergence and spread of antimicrobial resistance.

Genetic variations in toll-like receptor 4 in Mexican-Mestizo patients with intra-abdominal infection and/or pneumonia.

Sepsis is a leading cause of death around the world, and 73-83% of all sepsis cases requiring attention in intensive care units are linked to intra-abdominal infection (IAI) or pneumonia. The activation of innate immunity is central to the manifestation of sepsis, and toll-like receptor (TLR) 4 plays an important role in this activation process. The 299G and 399I alleles of TLR4 have been linked with an increased risk of Gram-negative bacteria (GNB) infections and septic shock in some populations. This case-control study evaluated the prevalence of D299G/T399I polymorphisms in Mexican patients with IAI and/or pneumonia and in healthy controls. Genotyping revealed that 1 in 44 patients (2.3%; CI 95%: 0.05-12.0%) and 4 in 126 controls (3.2%; CI 95%: 0.9-7.9%) were heterozygous for both the D299G and T399l polymorphisms (OR: 0.71, CI 95%: 0.01-7.44, p = NS), confirming the co-segregation of these alleles in this population. Furthermore, the patients with a GNB infection and severe sepsis were not carriers of the risk alleles. In summary, this report shows that the frequency of the D299G and T399I polymorphisms in Mexican-Mestizos is lower than anticipated in comparison with other ethnic groups, emphasizing the variable distribution of TLR4 polymorphisms among different populations. Consequently, this study was not able to detect associations between TLR4 polymorphisms and sepsis in this population.

Acute Cholangitis After Bilioenteric Anastomosis for Bile Duct Injuries.

Background/PurposeThe study aims to describe the clinical features, microbiology, and associated factors of acute cholangitis (AC) after bilioenteric anastomosis (BEA) for biliary duct injury (BDI). Additionally, we assessed the performance of the Tokyo Guidelines 2013 (TG13) recommendations in these patients.MethodsWe conducted a case-control study of 524 adults with a history of BEA for BDI from January 2000 to January 2014. A propensity score adjustment was performed for the analysis of the independent role of the main factors identified during the univariate logistic regression procedure.ResultsWe identified 117 episodes of AC in 70 patients; 51.3% were definitive AC according to the TG13 diagnostic criteria, and 39.3% did not fulfill the imaging criteria of AC. A history of post-operative biliary complications (OR 2.55, 95% CI 1.38–4.70) and the bile duct confluence preservation (OR 0.46, 95% CI 0.24–0.87) were associated with AC. Eighty-nine percent of the microorganisms were Enterobacteriaceae; of them, 28% were extended spectrum β-lactamase (ESBL) producers.ConclusionsAC is a common complication after BEA and must be suspected even in the absence of imaging findings, particulary in patients with a history of post-operative biliary complications, and/or without bile duct confluence preserved. An empirical treatment for ESBL-producing Enterobacteriaceae may be appropriate in patients living in countries with a high rate of bacterial drug resistance.