Single-Stage Posterior Vomerine Ostectomy, Premaxillary Setback, Bilateral Gingivoperiosteoplasties and Primary Bilateral Cheiloplasty in Patients with Protuberant Premaxilla.

Various patients with complete bilateral cleft lip and palate present with a protruded premaxilla. Several techniques have been described for correctional repair of the projection with a plethora of unsatisfactory outcomes. This poses a challenge not only for the cleft team providing care but also for the patients and their respective families. Multiple patients suffer from residual deformities after inadequate primary repair, which increase surgical, financial, and psychological burden. Premaxillary setback with posterior vomerine ostectomy and complete bilateral cleft lip repair can promote alignment of the premaxilla with the maxillary prominences. To effectively address this challenging deformity, we describe a single-stage surgical technique that includes vomerine ostectomy posterior to the vomero-premaxillary suture, bilateral gingivoperiosteoplasties with complete bilateral cleft lip repair, and primary cleft rhinoplasty. Careful surgical planning is essential for adequate matching between the length of the protruded premaxilla and the extent of ostectomy. The described technique offers several advantages for the management of complete bilateral cleft lip with a projected premaxilla. It can be applied anywhere around the world and is most beneficial in underprivileged areas where patients suffer from restricted access to healthcare, absence of presurgical orthodontics and lack of sufficient resources.

Prevalence of risk factors associated with development of capsular contracture after placement of breast implants.

OBJECTIVE: To determinate the prevalence of the main risk factors associated with development of capsular contracture after placement of breast implants in a referral center. METHOD: Retrospect study on 210 patients where sociodemographic variables, Baker's clinical scale and histopathological results were recorded. RESULTS: Statistical analysis of 210 patients was performed; 98.1% were women. The average age was 47 years (± 11), body mass index 25 (± 10) and onset of symptoms 13 years (± 8.5). Sociodemographic factors: domestic work 63.3%. Alcoholism 70% and smoking 65.7%. The main reason for consultation was pain plus deformity in 81.6%. The risk factors with statistical significance were the history of trauma, with 83.3% (p = 0.004), and the subglandular plane, with 73.8% (p = 0.0115). Histopathology: fibrous capsule 81.4%. CONCLUSIONS: The prevalence of the risk factors described are similar to those reported in the literature. Only for the history of trauma and the subglandular plane there was statistical significance.

OBJETIVO: Determinar la prevalencia de los principales factores de riesgo asociados a contractura capsular posterior a mamoplastia de aumento en un centro de referencia. MÉTODO: Estudio retrospectivo de 210 pacientes en el que se registraron variables sociodemográficas, escala clínica de Baker y resultados histopatológicos. RESULTADOS: Se realizó el análisis estadístico de 210 pacientes; el 98.1% fueron mujeres. La edad promedio fue de 47 años (± 11), el índice de masa corporal 25 kg/m2 (± 10) y el inicio de los síntomas 13 años (± 8.5). Factores sociodemográficos: labores domésticas 63.3%. Alcoholismo 70% y tabaquismo 65.7%. El principal motivo de consulta fue dolor más deformidad, en el 81.6%. Los factores de riesgo con significancia estadística fueron el antecedente de traumatismo, con un 83.3% (p = 0.004), y el plano subglandular, con un 73.8% (p = 0.0115). Histopatología: cápsula fibrosa 81.4%. CONCLUSIONES: La prevalencia de los factores de riesgo descritos es similar a lo reportado en la literatura. Solo para el antecedente de traumatismo y el plano subglandular hubo significancia estadística.

Correlation of liver fibrosis quantification by morphometry using HepaScan with the analysis of liver biopsies. A pilot study.

BACKGROUND: The gold standard for determining the degree of liver fibrosis (LF) continues to be biopsy evaluation. There are morphometry techniques that allow LF to be quantified on histopathological studies. OBJECTIVE: To measure the correlation between LF histological evaluation and fibrosis percentage (FP) morphometric quantification using the HepaScan software. MATERIAL AND METHODS: Observational, analytical, cross-sectional, prospective, prolective pilot study in which liver histological sections from 29 people who died from some liver disease and from 22 people who died from other causes (controls) were analyzed. FP was calculated with HepaScan on digital photographs of histological sections stained with the Masson technique, comparing it with the diagnosis established by three expert pathologists. RESULTS: Four-hundred and one images from the group with liver disease and 250 from the control group were analyzed. Inter-observer agreement had a kappa index of 0.329. There were FP statistically significant differences (p = 0.0001) between histopathological classification groups. HepaScan predictive capacity based on the area under the receiver operating characteristic curve was 0.983, 0.812, and 0.895 for mild, moderate, and severe fibrosis, respectively. CONCLUSIONS: HepaScan showed very good performance for evaluating FP in histological sections, which is why it can contribute to qualitative pathological diagnosis.

ANTECEDENTES: El estándar de oro para determinar el grado de fibrosis hepática (FH) continúa siendo la evaluación de la biopsia. Existen técnicas de morfometría que permiten cuantificar la FH en estudios histopatológicos. OBJETIVO: Medir la correlación entre la evaluación histológica de FH y la cuantificación por morfometría del porcentaje de fibrosis (PF) mediante HepaScan. MATERIAL Y MÉTODOS: Estudio piloto observacional, analítico, transversal, prospectivo y prolectivo en el que se analizaron cortes histopatológicos de hígado de 29 personas fallecidas por alguna hepatopatía y 22 personas fallecidas por otras causas (controles). El PF se calculó con HepaScan en fotografías digitales de cortes histológicos teñidos con la técnica Masson, comparándolo con el diagnóstico de tres patólogos expertos. RESULTADOS: Fueron analizadas 401 imágenes del grupo con hepatopatía y 250 del grupo de control. La concordancia interobservador tuvo un índice kappa de 0.329. Entre los grupos de clasificación histopatológica existieron diferencias estadísticas en el PF (p = 0.0001). La capacidad predictiva de HepaScan con base en el área bajo la curva característica operativa del receptor fue de 0.983, 0.812 y 0.895 para fibrosis leve, moderada y severa, respectivamente. CONCLUSIONES: HepaScan mostró muy buen desempeño para evaluar el PF en cortes histológicos, por lo que puede coadyuvar al diagnóstico patológico cualitativo.

The role of corticosteroids in patients hospitalized for COVID-19 at Mexico general Hospital.

OBJECTIVE: To compare the evolution of hospitalized patients infected with SARS-CoV-2 who received corticosteroid-based treatment versus patients who received standard therapy. METHOD: Retrospective, observational, and analytical study. Clinical records were collected from the different intensive care units, and data were obtained from confirmed COVID-19 patients over 18 years of age who were hospitalized. The population was divided into two groups: patients who received corticosteroid treatment, and those who received standard therapy. RESULTS: A total of 1603 patients were admitted to hospital, and of these 984 (62.9%) were discharged due to death. The main result was the identification by odds ratio (OR: 4.68; 95% confidence interval [95% CI]: 3.75-5.83; p = 0.001) as risk for death to the use of systemic steroids, as well as the use of invasive mechanical ventilation (OR: 2.26; 95% CI: 1.80-2.82; p < 0.001). The male gender was the most affected with 1051 (65.6%) patients. Mean age was 56 years (± 14). CONCLUSIONS: Corticosteroid use was associated with poor prognosis in patients hospitalized for COVID-19 compared to those receiving standard therapy.

OBJETIVO: Comparar la evolución de los pacientes hospitalizados infectados por SARS-CoV-2 que recibieron tratamiento a base de corticoesteroides frente a los pacientes que recibieron la terapia estándar. MÉTODO: Estudio de tipo retrospectivo, observacional y analítico. Se recolectaron los expedientes clínicos de las diferentes unidades de terapia intensiva y se obtuvieron datos de los pacientes confirmados de COVID-19, mayores de 18 años, que estuvieron hospitalizados. Se dividió la población en dos grupos: pacientes que recibieron tratamiento con corticoesteroides y pacientes que recibieron terapia estándar. RESULTADOS: De un total de 1603 pacientes ingresados a hospitalización, 984 (62.9%) fallecieron. El resultado principal fue la identificación mediante razón de momios (odds ratio [OR]: 4.68; intervalo de confianza del 95% [IC95%]: 3.75-5.83; p = 0.001) como riesgo para defunción con uso de esteroides sistémicos, así como con uso de ventilación mecánica invasiva (OR: 2.26; IC95%: 1.80-2.82; p < 0.001). El sexo masculino fue el más afectado, con 1051 (65.6%) pacientes. La media de edad fue de 56 años (± 14). CONCLUSIONES: El uso de corticoesteroides se asoció con mal pronóstico en los pacientes hospitalizados por COVID-19, en comparación con los que recibieron la terapia estándar.

Correlación de la cuantificación de fibrosis hepática por morfometría mediante HepaScan con el análisis de las biopsias hepáticas. Estudio piloto / Correlation of liver fibrosis quantification by morphometry using HepaScan with the analysis of liver biopsies. A pilot study

Resumen Antecedentes: El estándar de oro para determinar el grado de fibrosis hepática (FH) continúa siendo la evaluación de la biopsia. Existen técnicas de morfometría que permiten cuantificar la FH en estudios histopatológicos. Objetivo: Medir la correlación entre la evaluación histológica de FH y la cuantificación por morfometría del porcentaje de fibrosis (PF) mediante HepaScan. Material y métodos: Estudio piloto observacional, analítico, transversal, prospectivo y prolectivo en el que se analizaron cortes histopatológicos de hígado de 29 personas fallecidas por alguna hepatopatía y 22 personas fallecidas por otras causas (controles). El PF se calculó con HepaScan en fotografías digitales de cortes histológicos teñidos con la técnica Masson, comparándolo con el diagnóstico de tres patólogos expertos. Resultados: Fueron analizadas 401 imágenes del grupo con hepatopatía y 250 del grupo de control. La concordancia interobservador tuvo un índice kappa de 0.329. Entre los grupos de clasificación histopatológica existieron diferencias estadísticas en el PF (p = 0.0001). La capacidad predictiva de HepaScan con base en el área bajo la curva característica operativa del receptor fue de 0.983, 0.812 y 0.895 para fibrosis leve, moderada y severa, respectivamente. Conclusiones: HepaScan mostró muy buen desempeño para evaluar el PF en cortes histológicos, por lo que puede coadyuvar al diagnóstico patológico cualitativo.

Abstract Background: The gold standard for determining the degree of liver fibrosis (LF) continues to be biopsy evaluation. There are morphometry techniques that allow LF to be quantified on histopathological studies. Objective: To measure the correlation between LF histological evaluation and fibrosis percentage (FP) morphometric quantification using the HepaScan software. Material and methods: Observational, analytical, cross-sectional, prospective, prolective pilot study in which liver histological sections from 29 people who died from some liver disease and from 22 people who died from other causes (controls) were analyzed. FP was calculated with HepaScan on digital photographs of histological sections stained with the Masson technique, comparing it with the diagnosis established by three expert pathologists. Results: Four-hundred and one images from the group with liver disease and 250 from the control group were analyzed. Inter-observer agreement had a kappa index of 0.329. There were FP statistically significant differences (p = 0.0001) between histopathological classification groups. HepaScan predictive capacity based on the area under the receiver operating characteristic curve was 0.983, 0.812, and 0.895 for mild, moderate, and severe fibrosis, respectively. Conclusions: HepaScan showed very good performance for evaluating FP in histological sections, which is why it can contribute to qualitative pathological diagnosis.

Machine learning and deep learning predictive models for type 2 diabetes: a systematic review.

Diabetes Mellitus is a severe, chronic disease that occurs when blood glucose levels rise above certain limits. Over the last years, machine and deep learning techniques have been used to predict diabetes and its complications. However, researchers and developers still face two main challenges when building type 2 diabetes predictive models. First, there is considerable heterogeneity in previous studies regarding techniques used, making it challenging to identify the optimal one. Second, there is a lack of transparency about the features used in the models, which reduces their interpretability. This systematic review aimed at providing answers to the above challenges. The review followed the PRISMA methodology primarily, enriched with the one proposed by Keele and Durham Universities. Ninety studies were included, and the type of model, complementary techniques, dataset, and performance parameters reported were extracted. Eighteen different types of models were compared, with tree-based algorithms showing top performances. Deep Neural Networks proved suboptimal, despite their ability to deal with big and dirty data. Balancing data and feature selection techniques proved helpful to increase the model's efficiency. Models trained on tidy datasets achieved almost perfect models.

Anakinra versus Baricitinib: Different Strategies for Patients Hospitalized with COVID-19.

BACKGROUND: Immunomodulatory drugs have been used in patients with severe COVID-19. The objective of this study was to evaluate the effects of two different strategies, based either on an interleukin-1 inhibitor, anakinra, or on a JAK inhibitor, such as baricitinib, on the survival of patients hospitalized with COVID-19 pneumonia. METHODS: Individuals admitted to two hospitals because of COVID-19 were included if they fulfilled the clinical, radiological, and laboratory criteria for moderate-to-severe disease. Patients were classified according to the first immunomodulatory drug prescribed: anakinra or baricitinib. All subjects were concomitantly treated with corticosteroids, in addition to standard care. The main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital death. Statistical analysis included propensity score matching and Cox regression model. RESULTS: The study subjects included 125 and 217 individuals in the anakinra and baricitinib groups, respectively. IMV was required in 13 (10.4%) and 10 (4.6%) patients, respectively (p = 0.039). During this period, 22 (17.6%) and 36 (16.6%) individuals died in both groups (p = 0.811). Older age, low functional status, high comorbidity, need for IMV, elevated lactate dehydrogenase, and use of a high flow of oxygen at initially were found to be associated with worse clinical outcomes. No differences according to the immunomodulatory therapy used were observed. For most of the deceased individuals, early interruption of anakinra or baricitinib had occurred at the time of their admission to the intensive care unit. CONCLUSIONS: Similar mortality is observed in patients treated with anakinra or baricitinib plus corticosteroids.

Mano diabética en el Hospital General de México "Dr. Eduardo Liceaga": experiencia en 42 casos / Diabetic hand in Hospital General de México "Dr. Eduardo Liceaga": experience in 42 cases

INTRODUCCIÓN Y OBJETIVO: El término mano diabética describe las infecciones de mano graves resultantes de trauma, mordedura humana o de perro y abuso de drogas, en pacientes que padecen diabetes mellitus. Las manifestaciones clínicas más frecuentes son celulitis, paroniquia, tenosinovitis, absceso profundo, artritis séptica y osteomielitis. Nuestra finalidad es presentar nuestra experiencia en la atención de pacientes con mano diabética, debido a que el retraso del diagnóstico de esta patología dificulta su tratamiento y predispone a mayores complicaciones. MATERIAL Y MÉTODO: Realizamos un estudio retrospectivo sobre los casos de mano diabética atendidos en el Servicio de Cirugía Plástica y Reconstructiva del Hospital General "Eduardo Liceaga" de la Ciudad de México (México) entre marzo de 2013 y marzo de 2018. RESULTADOS: El intervalo de edad de los pacientes fue de 19 a 87 años, con un número total de 42 pacientes atendidos, 23 mujeres (55%) y 19 varones (45%). Veinticinco pacientes (60%) no referían antecedentes de cirugías previas en mano y 17 (40%) presentaban antecedentes quirúrgicos tales como: amputación supracondílea en 4 pacientes (10%), amputación infracondílea en 1 paciente (2%) y remodelación de dedos en el 7%. El diagnóstico más frecuente fue tenosinovitis infecciosa de 3er dedo. El patógeno más frecuentemente encontrando fue Enterobacter cloacae (14%). Al analizar los tipos de tratamiento quirúrgico utilizados, específicamente la amputación, hubo diferencias sobresalientes al realizar el contraste por género y valorar la presencia de obesidad en los pacientes. El 52% de las mujeres sufrió amputación frente al 21% de varones (p = .029 a través de X2 de Pearson). El 43% de los pacientes con obesidad fueron amputados en comparación con el 36% que no la padecían (p = .061 a través de X2 de Pearson). CONCLUSIONES: En nuestra experiencia, se trata de una patología con una alta incidencia; sin embargo, no contamos en general con literatura suficiente para determinar un diagnóstico oportuno y un tratamiento eficaz, al igual que tampoco disponemos de un algoritmo o clasificación que ayude al control y seguimiento de los pacientes

BACKGROUND AND OBJECTIVE: The term diabetic hand describes serious hand infections resulting from trauma, human or dog bite and drug abuse, in patients suffering from diabetes mellitus. The most frequent clinical manifestations are cellulitis, paronychia, tenosynovitis, Deep abscess, septic arthritis and osteomyelitis. We present our experience in the care of patients with diabetic hand, as the delay of diagnosis makes the treatment difficult and predisposes to greater complications. METHODS: A retrospective study was conducted on cases of diabetic hand in Plastic and Reconstructive Surgery Department at Hospital General "Dr. Eduardo Liceaga" in Mexico City (Mexico) from March 2013 to March 2018. RESULTS: The age range of the patients was from 19 to 87 years, having a total number of 42 patients, 23 female (55%) and 19 male (45%). Twenty-five patients (60%) did not report a history of surgery, meanwhile 17 (40%) had a surgical history: supracondylar amputation was found in 4 patients (10%) and infracondylar amputation in 1 patient (2%); remodelation of the finger was equivalent to 7%. The most frequent diagnosis was infectious tenosynovitis of 3rd finger. The pathogen most frequently found was Enterobacter cloacae (14%). When analyzing the types of surgical treatment used, specifically amputation, there were outstanding differences when contrasting by gender and the presence of obesity in the patients: 52% of the female gender were amputated against 21% of the male group (p = .029 through Pearson's X2); 43% of patients with obesity were amputed compared to 36% who did not have it (p = .061 through Pearson's X2). CONCLUSIONS: This pathology has a high incidence, however there is not enough literature to determine timely diagnosis and effective treatment, as there is yet no algorithm or some classification that helps the control and monitoring of patients

Prevalencia y factores asociados a la colonización por Staphylococcus aureus resistente a meticilina en centros de larga estancia en el sur de España / Prevalence and risk factors of methicillin-resistant Staphylococcus aureus colonization among residents living in long-term care facilities in southern Spain

Introducción: Staphylococcus aureus (S. aureus) resistente a meticilina (SARM) se ha convertido en el principal problema de salud pública que causan los microorganismos multirresistentes. Los centros de larga estancia (CLE) constituyen un reservorio importante de SARM. Los objetivos de este estudio fueron determinar la prevalencia y los factores relacionados con la colonización por SARM en los sujetos residentes en CLE en el sur de España. Metodología Estudio transversal descriptivo en el que se incluyeron a los sujetos ingresados en 17 CLE entre el 1 de abril de 2009 y el 30 de junio de 2010. Se realizó una toma de muestra con torunda de ambas fosas nasales con cultivo posterior en medio cromogénico. Si hubo crecimiento bacteriano compatible con estafilococo, se realizó la prueba de coagulasa con el test de aglutinación en látex. Se utilizó un sistema automático para la identificación y sensibilidad del estafilococo aislado. Se construyó un modelo de regresión logística donde la variable primaria del estudio, el ser portador de SARM, fue incluida como variable dependiente y se incluyeron como covariables todas aquellas que en el análisis bivariado hubiesen mostrado un nivel de significación inferior a 0,2. Los individuos fueron clasificados en portador de SARM, S. aureus meticilín-sensible y no portador. Resultados Se incluyeron 744 individuos. Cuatrocientas ochenta y uno (65%) eran mujeres. La edad mediana (Q1-Q3) fue de 81 (74-86) años. Setenta y nueve (10,6%) y 67 (9%) sujetos estaban colonizados por (..) (AU)

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important problem related to multiresistant microorganisms in the health care system. Long-term-care facilities (LTCFs)are one of the main reservoirs of this microorganism. The objective of our study was to determine the prevalence and factors associated with MRSA colonization among subjects living in LTCFs in southern Spain. Methods: During the period from 1st April 2009 to 30th June 2010, all subjects living in 17 LTCFs of our area were included in a cross-sectional study. Patients were screened by using nasal swabs and these were cultured in a chromogenic media. Suspected S. aureus colonies were identified by the latex agglutination test. Testing for antimicrobial identification and susceptibility was performed by an automated system.A logistic regression model was built, in which to be colonized by MRSA was the dependent variable, and covariates were entered if a difference with P < .2 was detected in the bivariate analysis. Residents were classified as MRSA carriers, methicillin-susceptible S. aureus carriers and non-carriers. Results: Seven hundreds and forty-four subjects were included. There were 481 (65%) females. The median (Q1-Q3) age was 81 (74-86) years. Seventy-nine (10.6%) and 67 (9%) were colonized by MRSA and methicillin-susceptible S. aureus, respectively. Significant risk factors for MRSA carriers were recentantibiotic use, previous hospital admission in the last three months, a high comorbidity measured by Charlson index and a history of colonization by MRSA. Conclusions: The prevalence of MRSA colonization in the LTCFs of our area is similar to that described in others European countries. In our institutions, subjects with recent antibiotic use, a high comorbidity, a history of MRSA colonization and a hospital admission in the last three months are more susceptible to be colonized by MRSA (AU)

[Prevalence and risk factors of methicillin-resistant Staphylococcus aureus colonization among residents living in long-term care facilities in southern Spain]. / Prevalencia y factores asociados a la colonización por Staphylococcus aureus resistente a meticilina en centros de larga estancia en el sur de España.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important problem related to multiresistant microorganisms in the health care system. Long-term-care facilities (LTCFs) are one of the main reservoirs of this microorganism. The objective of our study was to determine the prevalence and factors associated with MRSA colonization among subjects living in LTCFs in southern Spain. METHODS: During the period from 1st April 2009 to 30th June 2010, all subjects living in 17 LTCFs of our area were included in a cross-sectional study. Patients were screened by using nasal swabs and these were cultured in a chromogenic media. Suspected S. aureus colonies were identified by the latex agglutination test. Testing for antimicrobial identification and susceptibility was performed by an automated system. A logistic regression model was built, in which to be colonized by MRSA was the dependent variable, and covariates were entered if a difference with P<.2 was detected in the bivariate analysis. Residents were classified as MRSA carriers, methicillin-susceptible S. aureus carriers and non-carriers. RESULTS: Seven hundreds and forty-four subjects were included. There were 481 (65%) females. The median (Q1-Q3) age was 81 (74-86) years. Seventy-nine (10.6%) and 67 (9%) were colonized by MRSA and methicillin-susceptible S. aureus, respectively. Significant risk factors for MRSA carriers were recent antibiotic use, previous hospital admission in the last three months, a high comorbidity measured by Charlson index and a history of colonization by MRSA. CONCLUSIONS: The prevalence of MRSA colonization in the LTCFs of our area is similar to that described in others European countries. In our institutions, subjects with recent antibiotic use, a high comorbidity, a history of MRSA colonization and a hospital admission in the last three months are more susceptible to be colonized by MRSA.

Baseline serum low-density lipoprotein cholesterol levels predict response to hepatitis C virus therapy in HIV/hepatitis C virus coinfected patients.

BACKGROUND: High levels of serum low-density lipoprotein cholesterol are associated with better response to pegylated interferon and ribavirin in hepatitis C virus monoinfected patients. There are no data concerning this topic in HIV/hepatitis C virus coinfected patients in whom lipid disorders are particularly common. OBJECTIVE: To assess the association between baseline lipid levels and sustained virologic response to pegylated interferon and ribavirin in coinfected patients. METHODS: A total of 260 HIV/hepatitis C virus coinfected patients under treatment with pegylated interferon and ribavirin and who had a baseline serum lipid profile were included in this retrospective study. RESULTS: Thirty-eight (24%) patients with genotypes 1-4 and 64 (63%) with genotypes 2-3 achieved sustained virologic response. Forty-nine (44%) patients with serum low-density lipoprotein cholesterol levels 100 mg/dl or more showed sustained virologic response compared with 53 (36%) with lower values [adjusted odds ratio: 2.51; 95% confidence interval: 1.40-4.87; P = 0.003]. This association was independent of the remaining predictors of sustained virologic response which were genotypes 2-3, plasma hepatitis C virus RNA 600,000 IU/ml or less, exposure to at least 80% of the planned therapy and lack of concomitant antiretroviral therapy. The rate of sustained virologic response in patients with genotype 1 and low-density lipoprotein cholesterol at least 100 mg/ml was 31% compared with 17% in those with lower values (adjusted odds ratio: 2.19; 95% confidence interval: 1.04-4.66; P = 0.040). The corresponding figures in subjects with genotypes 2-3 were 73 and 58% [2.71 (0.99-7.46); P = 0.054]. No other lipid was associated with response. CONCLUSION: Higher low-density lipoprotein cholesterol levels predict sustained virologic response to pegylated interferon and ribavirin in HIV/hepatitis C virus coinfected patients. This might be used to improve the rate of sustained virologic response in this setting.

Influence of concomitant antiretroviral therapy on the rate of sustained virological response to pegylated interferon plus ribavirin in hepatitis C virus/HIV-coinfected patients.

OBJECTIVES: To investigate whether concomitant antiretroviral therapy (ART) is a predictor of sustained virological response (SVR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with pegylated interferon plus ribavirin. METHODS: Three hundred and ten HIV/HCV-coinfected patients on pegylated interferon plus ribavirin treatment, 258 of them with concurrent ART, were included in this retrospective multicentre study. The predictors of SVR were evaluated. RESULTS: SVR was shown by 114 (37%) subjects. HCV genotype 2 or 3, plasma HCV-RNA load lower than 600 000 IU/mL, an exposure to the therapy against HCV infection > or =80% of the planned dose and baseline CD4 cell counts higher than or equal to 300/mm(3) were predictors of SVR. Likewise, patients without ART and those receiving a combination including tenofovir or stavudine plus lamivudine plus a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) showed a higher SVR rate than the subjects who were on other ART strategies at baseline [44%, 44% and 29%, respectively; adjusted odd ratio (95% CI) for no ART = 1.96 (1.07-4.76), P = 0.025, and for ART including tenofovir or stavudine plus lamivudine plus a PI or a NNRTI = 2.08 (1.16-3.70), P = 0.014]. CONCLUSIONS: The ART strategy on starting therapy with pegylated interferon plus ribavirin is a predictor of SVR in HIV/HCV-coinfected patients. Subjects without ART and those receiving combinations of a PI or a NNRTI with a nucleos(t)ide backbone of tenofovir or stavudine plus lamivudine respond better than those who receive other regimens.

Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy.

UNLABELLED: Little is known about the natural history of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected subjects under highly active antiretroviral therapy (HAART). The objectives of this study were to obtain information about the mortality, the incidence of hepatic decompensations, and the predictors thereof in this population. In a multicenter cohort study, the time to the first hepatic decompensation and the survival of 1,011 antiretroviral naïve, HIV/HCV-coinfected patients who started HAART and who were followed prospectively were analyzed. After a median (Q1-Q3) follow-up of 5.3 (2.9-7.1) years, 59(5.83%) patients developed a hepatic decompensation and 69 (6.82%) died, 30 (43%) of them because of liver disease. The factors independently associated [HR (95% CI)] with the occurrence of hepatic decompensations were age older than 33 years [2.11 (1.18-3.78)], female sex [2.11 (1.07-4.15)], Centers for Disease Control stage C [2.14 (1.24-3.70)], a diagnosis of cirrhosis at baseline [10.86 (6.02-19.6)], CD4 cell gain lower than 100/mm3 [4.10 (2.18-7.69)] and less than 60% of the follow-up with undetectable HIV viral load [5.23 (2.5-10.93)]. Older age [2.97 (1.18-7.50)], lack of HCV therapy [11.32 (1.44-89.05)], hepatitis D virus coinfection [16.15 (2.45-106.48)], a diagnosis of cirrhosis at recruitment [13.69 (5.55-34.48)], hepatic encephalopathy [62.5 (21.27-200)] and lower CD4 cell gain [3.63 (1.45-9.09)] were associated with mortality due to liver failure. CONCLUSION: End-stage liver disease is the primary cause of death in HIV/HCV-coinfected patients under HAART. Higher increase of CD4 cell counts, lack of markers of serious liver disease and therapy against HCV are factors associated with better hepatic outcome.

Low-level liver enzyme elevations during HAART are not associated with liver fibrosis progression among HIV/HCV-coinfected patients.

OBJECTIVES: To assess the association between non-severe liver enzyme elevations (LEEs) during antiretroviral treatment and liver fibrosis in HIV/HCV-coinfected patients. METHODS: All co-infected patients from an Infectious Disease Unit who had received treatment with highly active antiretroviral therapy (HAART) for at least 12 months before undergoing a liver biopsy were included in the study. RESULTS: One-hundred and sixteen patients met the inclusion criteria of the study. Advanced liver fibrosis was observed in 32 (38%) of 84 patients who developed non-severe LEEs and in 11 (34%) of 32 subjects who developed severe (grade > or = 3) LEEs, (P = 0.7). Seven (6%) of 116 patients showed grade 3 or 4 LEEs for at least 30% of the follow-up. Advanced liver fibrosis was observed in five (71%) of these patients and in 38 (35%) of the 109 subjects who did not develop long-term severe LEEs (P = 0.05). Eight (10%) of 84 patients showed grade 2 LEEs for at least 30% of the follow-up. Advanced liver fibrosis was observed in 28 (37%) of 76 subjects who did not develop long-term grade 2 LEEs and in three (38%) of eight patients who developed them (P = 0.9). CONCLUSIONS: In HIV/HCV-coinfected patients, non-severe LEEs, whether persistent or not, are not associated with advanced liver fibrosis. On the other hand, long-term severe LEEs are associated with more severe liver fibrosis in this population.

Use of noninvasive markers to detect Leishmania infection in asymptomatic human immunodeficiency virus-infected patients.

Visceral leishmaniasis (VL) caused by Leishmania infantum is a common disease in human immunodeficiency virus (HIV)-infected people in the Mediterranean basin. However, most such cases are asymptomatic, and little information about the prevalence of these infections in HIV-infected individuals is available. The aim of this study was to assess the prevalence of subclinical infection and the relationship between several Leishmania infection markers by noninvasive methods in asymptomatic HIV-infected patients from Southern Spain. Ninety-two HIV-infected patients, who were consecutively attended at the participant hospitals in 2004, were invited to participate in this study. These patients were asymptomatic and without any history of cutaneous or visceral leishmaniasis. Leishmania kinetoplast DNA (kDNA) was amplified from peripheral blood samples from 28 (30.4%) of these HIV-infected subjects. Sera from three (3.5%) patients tested positive for Leishmania by an enzyme-linked immunoassay. Two patients (2.4%) showed a specific 16-kDa band by Western blotting. In contrast, none of the patients showed a positive agglutination of urine. The leishmanin skin test was positive for four (4.3%) patients. None of the patients with a PCR-positive result showed a positive reaction by enzyme-linked immunoassay or by specific bands in Western blotting or had a positive leishmanin skin test. In conclusion, L. infantum kDNA was detected in a large proportion of asymptomatic HIV-infected patients, although a demonstrable cellular or humoral immune response to this parasite was not shown. Conversely, Leishmania antigen in urine was not detected in these patients.

Survival and prognostic factors of HIV-infected patients with HCV-related end-stage liver disease.

OBJECTIVE: To find the survival and the predictors of death of HIV-infected patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD). DESIGN AND METHODS: A prospective cohort study set in the infectious diseases units of four tertiary care public hospitals in Andalucía, Spain. From a multicentric cohort of 2664 HIV/HCV-co-infected patients, all consecutive patients with HCV-related cirrhosis who presented with the first hepatic decompensation from January 1997 to June 2004 were followed-up and 153 patients were included. The survival and the demographic, HIV-related and liver-related factors associated with death were evaluated. RESULTS: Ninety-five (62%) patients died during the follow-up. In 79 (85%) individuals, the cause of death was liver related. The median survival time was 13 months. Independent predictors of survival were Child score [hazard ratio (HR), 1.2; 95% confidence interval (CI), 1.08-1.37; P = 0.001], CD4+ cell count at decompensation lower than 100 cells/microl (HR, 2.48; 95% CI, 1.52-4.06; P < 0.001) and hepatic encephalopathy as the first hepatic decompensation (HR, 2.45; 95% CI, 1.41-4.27; P = 0.001). HAART was prescribed to 101 (66%) patients. The cumulative probability of survival in patients under HAART was 60% at 1 year and 40% at 3 years, versus 38 and 18%, respectively, in patients not treated with HAART (P < 0.0001). The HR (95% CI) of death in patients on HAART was 0.5 (0.3-0.9), (P = 0.03). CONCLUSIONS The survival of HIV/HCV-co-infected patients with ESLD is extremely poor. Immunosuppression and markers of severe liver disease predict liver-related mortality in these patients. HAART seems to be associated with a reduced liver-related mortality.

Incidence of and factors associated with hepatocellular carcinoma among hepatitis C virus and human immunodeficiency virus coinfected patients with decompensated cirrhosis.

We compared the incidence of and factors associated with hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%) HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001) patients in the former and in the latter group, respectively, showed HCC. Fifty-four (11%) patients without HCC at baseline developed such a disease during follow-up. There were no incident cases among the HIV-coinfected population. The density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95% IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5 (1.1-5)] were the only two independent predictors of the emergence of HCC. In the group of patients in whom the date of HCV infection could be estimated, the time elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The incidence of HCC in patients with HCV-related cirrhosis after the first hepatic decompensation is lower in HIV-coinfected patients. This is probably due to the fact that HIV infection shortens the survival of HCV-coinfected patients with end-stage liver disease to such an extent that HCC not had a chance to emerge.

Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection.

BACKGROUND: Chronic hepatitis C disease (CHC) follows an accelerated course in human immunodeficiency virus (HIV) coinfection. The reasons for this are unclear. Fas-mediated hepatocyte apoptosis is involved in the pathogenesis of hepatitis C virus (HCV) infection. We sought to compare the expression of Fas on hepatocytes and irreversible apoptosis of hepatocytes among patients with CHC with and without HCV/HIV coinfection. METHODS: Fas-immunostained hepatocytes were semiquantified, and apoptotic hepatocytes were detected by staining caspase-cleaved cytokeratin 18 filaments and counted across the entire section of liver-biopsy specimens from HCV-infected patients with and without HCV/HIV coinfection. RESULTS: One hundred thirty-four HCV/HIV-coinfected and 100 HCV-infected patients were included. HCV/HIV coinfection was associated with both diffuse distribution of Fas-stained hepatocytes (adjusted odds ratio [AOR], 7.4 [95% confidence interval {CI}, 3.8-14.4]) and with apoptotic hepatocyte counts greater than the median (AOR, 2.5 [95% CI, 1.5-4.5]). In HCV/HIV-coinfected patients, CD4+ cell nadir<200 cells/mL was associated with both Fas expression (AOR, 2.9 [95% CI, 1.3-6.8]) and hepatocyte apoptosis (AOR, 2.3 [95% CI, 1.1-4.9]). CONCLUSION: HCV/HIV-coinfected patients show higher levels of hepatocytes expressing Fas and undergoing irreversible apoptosis than do HCV-infected patients. However, low CD4+ cell nadirs in coinfected patients are associated with hepatocyte Fas expression and apoptosis.

Transient rebounds of HIV plasma viremia are associated with the emergence of drug resistance mutations in patients on highly active antiretroviral therapy.

BACKGROUND: There are very few and contradictory data about the consequences of 'blips', transient rebounds of HIV viremia. We assessed the emergence of new drug resistance mutations during blips among HIV-infected patients on HAART from a cohort in which we found no association between blips and virological failure. METHODS: Seventeen patients with blips were selected from 330 patients under HAART for over 48 weeks according to these criteria: (1) presence of only one blip, viremia < or =1000copies/ml preceded by two consecutive visits and followed by one visit showing undetectable viremia; (2) therapy adherence > or =95%; (3) availability of frozen sera. RESULTS: HIV RNA could be extracted and amplified from five patients. In another two patients only the protease region could be amplified. Drug mutations in either the retrotranscriptase or protease genes, not detected at baseline, were observed in six patients at the blip. None of the patients showed detectable viremia during a median (range) follow-up after the blip of 120 (36-156) weeks. CONCLUSIONS: Transient rebounds of viremia in patients on HAART are associated with the emergence of new drug resistant HIV variants. In spite of it, virological failure is not observed after a median follow-up of over 2 years.

HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.