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.

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.

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.

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.

[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.

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.

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.

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.

Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine.

BACKGROUND: The hepatotoxicity of highly active antiretroviral therapy (HAART) could enhance liver fibrosis in HIV/Hepatitis C virus (HCV)-coinfected patients. Moreover, HAART-related immune restoration could lessen HCV-associated liver damage. The data on the effect of protease inhibitors (PI) on liver fibrosis are scant and contradictory. No information is available on the relationship between non-nucleoside analogue therapy and liver fibrosis in co-infected patients. OBJECTIVE: To investigate the associations between the use of different antiretroviral drugs and the liver fibrosis in patients with HIV and HCV infections. DESIGN: Cross-sectional study. METHODS: All HIV/HCV co-infected patients with an available liver biopsy and known or estimated duration of HCV infection seen at a Infectious Diseases Unit were included in the study. The fibrosis stage and the fibrosis progression rate were evaluated. RESULTS: The inclusion criteria were fulfilled by 152 patients. Age at HCV infection < 20 years [adjusted odds ratio (AOR), 0.39; 95% confidence interval (CI), 0.19-0.82], PI-based HAART (AOR, 0.39; 95% CI, 0.19-0.78) and nevirapine-based HAART (AOR, 2.56; 95% CI, 1.02-6.58) were associated with fibrosis stage >or= F3. The variables associated with fibrosis progression rate > 0.2 units/year were age at HCV infection < 20 years (AOR, 0.23; 95% CI, 0.1-0.52), CD4 cell counts < or = 250 x 10/l at liver biopsy (AOR, 2.8; 95% CI, 1.1-7.1), PI-based HAART (AOR, 0.39; 95% CI, 0.2-0.8) and nevirapine-based HAART (AOR, 3.82; 95% CI, 1.9-7.6). CONCLUSIONS: HAART regimens including nevirapine are associated with faster liver fibrosis progression in HIV-infected patients with chronic hepatitis C. In contrast, patients on PI as the backbone of potent antiretroviral therapy are more likely to show less liver fibrosis.

Transient rebounds of low-level viraemia among HIV-infected patients under HAART are not associated with virological or immunological failure.

OBJECTIVE: To analyse whether blips are associated with a higher risk of virological or immunological failure than persistent undetectable viraemia (UND) among HIV-infected patients receiving HAART. DESIGN: Retrospective cohort study. SUBJECTS: Patients with blips or UND were selected from a prospective cohort of 330 patients under HAART for over 48 weeks. Blips were defined as detectable viraemia up to a maximum of 1000 copies/ml preceded by two consecutive visits and followed by one visit showing undetectable viraemia. Patients were included according to the following criteria: i) Blip group: patients that showed transient relapses of viraemia; ii) UND group: patients who had achieved UND on HAART before 24 weeks of therapy and that sustained viral suppression for four consecutive visits. MAIN OUTCOME MEASURES: Virological and immunological failure. RESULTS: Thirty seven (11%) and 65 (20%) patients showed blips and persistent UND, respectively. Virological failure was observed in three (8.1%) patients in the blip group and 11 (16.9%) patients in the UND group (P=0.25). The time to virological failure was shorter in the UND group (P=0.12). The rates of virological failure and the time to virological failure were similar between both groups after excluding patients with compliance <95%. The time to immunological failure was also similar in both groups (P=0.5). In a Cox model, only the use of saquinavir hard gel-based regimens was independently associated with the time to virological and immunological failure. CONCLUSION: Patients under HAART with transient low-level viraemia are not at an increased risk of developing virological or immunological failure.

Detection of Leishmania infantum kinetoplast DNA in peripheral blood from asymptomatic individuals at risk for parenterally transmitted infections: relationship between polymerase chain reaction results and other Leishmania infection markers.

Individuals with frequent exposures to agents spread through the parenteral route show a high prevalence of Leishmania seropositivity in Spain. However, the frequency of positive polymerase chain reaction (PCR) results for Leishmania in blood in this setting remains unknown. In this study, L. infantum kinetoplast DNA (kDNA) was found in blood from 23 (24%) of 95 asymptomatic individuals with a serum Leishmania antibody titer > or = 1:20 and in none of 44 seronegative individuals. The greater the antibody titer, the greater the proportion of PCR-positive samples, but 16 (20%) of 81 individuals with antibody titers < or = 1:40 tested positive by PCR. Nine (37%) PCR-positive and 22 (19%) (P = 0.03) PCR-negative individuals showed a positive leishmanin skin test result. This results show that a remarkable proportion of asymptomatic Leishmania-seropositive individuals at risk for parenterally transmitted infections carry Leishmania kDNA in blood. This is more common in subjects with a high serum Leishmania antibody level and a positive leishmanin skin test result.

Necrotizing granulomatous vasculitis in advanced HIV infection.

We describe the first case of granulomatous necrotizing vasculitis not restricted to the central nervous system in an HIV-infected patient. No mycobacteria or drugs potentially associated with granuloma formation were involved in this patient, suggesting that the cause of this vasculitis was probably autoimmune. The development of granulomatous vascular inflammation in this patient with less than 200 CD4 cells/microl might have been due to immune overactivation. After starting potent antiretroviral therapy a profound immune deactivation was observed and the vasculitis did not relapse.

Lymphoepithelioma-like carcinoma of the uterine cervix.

CONTEXT: It has been proposed that Epstein-Barr virus (EBV) plays a role in the etiology of lymphoepithelioma-like carcinoma (LELC) in diverse anatomic locations. In contrast to Asian women, Western women have a low prevalence of LELC of the uterine cervix, and EBV genomes have not been identified. OBJECTIVE: To assess the presence of EBV in LELC of the uterine cervix in 4 white Western women. DESIGN: We collected 4 cases of LELC of the uterine cervix between 1990 and 2000. We performed histologic and immunohistochemical analyses of formalin-fixed, paraffin-embedded tumor samples. We amplified tumor DNA with polymerase chain reaction to detect EBV, human papillomavirus, and simian virus 40 DNAs. RESULTS: Immunohistochemically, tumor cells were positive for cytokeratins and showed strong expression of p53 and MIB-1. Staining for the oncoprotein c-Erb-B2 was focally positive, and staining for Bcl-2 and progesterone receptors was negative. Only one case showed focal nuclear staining for estrogen receptors. All cases had a dense infiltrate of mature lymphocytes expressing T-cell antigens CD45RO, CD3, and CD8. Polymerase chain reaction analysis did not detect EBV, human papillomavirus, or simian virus 40 DNA sequences in any of the 4 cases. One case had positive serologic results for anti-EBV antibodies, indicating a mild or chronic infection. CONCLUSIONS: LELC of the uterine cervix shows the immunohistochemical profile of an aggressive tumor in spite of its good prognosis, in which CD8 cytotoxic suppressor lymphocytes could play an important role. Based on our results, the role of EBV, human papillomavirus, or simian virus 40 in the pathogenesis of LELC of the uterine cervix in Western women remains unclear.

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.

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.