Cyclosporine A in addition to standard ART during primary HIV-1 infection: pilot randomized clinical trial.

Background: Initiating ART during acute/recent HIV-1 infection reduces viral reservoir formation. It has been proposed that, during this phase, the size of the viral reservoir could be further reduced by the association of immunomodulatory therapy with ART. Contradictory results have emerged, however, from two trials evaluating the impact on immune recovery and the viral reservoir of adding cyclosporine A to ART during primary HIV-1 infection. Patients and methods: Twenty patients with acute/recent HIV-1 infection were randomized to receive ART alone (tenofovir, emtricitabine and lopinavir/ritonavir) or associated with 8 weeks of cyclosporine A (0.3-0.6 mg/kg twice daily). The impact on viral load, immune response and integrated and non-integrated DNA viral reservoir at 0, 8 and 36 weeks of treatment was evaluated. Results: The estimated median time from HIV-1 infection to ART onset was 63 days (IQR 53; 79.5) with 90% of patients at Fiebig V stage. No significant differences were observed in viral load decay, CD4 T cell recovery, immune response markers or the evolution of integrated DNA at week 8 (end of cyclosporine A) and week 36 between groups. However, non-integrated DNA significantly increased in the cyclosporine A arm between weeks 0 and 36. Cyclosporine A was well tolerated. Conclusions: Adding cyclosporine A to ART during acute/recent infection did not improve immune recovery. However, unintegrated DNA increased in the cyclosporine A group, suggesting an anti-integration effect, a point warranting further research (ClinicalTrials.gov Identifier: NCT00979706).

Trends in Transmission of Drug Resistance and Prevalence of Non-B Subtypes in Patients with Acute or Recent HIV-1 Infection in Barcelona in the Last 16 Years (1997-2012).

OBJECTIVES: To evaluate the prevalence of transmitted drug resistance (TDR) and non-B subtypes in patients with acute/recent HIV-1 infection in Barcelona during the period 1997-2012. METHODS: Patients from the "Hospital Clínic Primary HIV-1 Infection Cohort" with a genotyping test performed within 180 days of infection were included. The 2009 WHO List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistance was used for estimating the prevalence of TDR and phylogenetic analysis for subtype determination. RESULTS: 189 patients with acute/recent HIV-1 infection were analyzed in 4 time periods (1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64). The proportion of patients with acute/recent HIV-1 infection with respect to the total of newly HIV-diagnosed patients in our center increased over the time and was 2.18%, 3.82%, 4.15% and 4.55% for the 4 periods, respectively (p=0.005). The global prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study period (p=0.2). The increase in the last period was driven by protease-inhibitor and nucleoside-reverse-transcriptase-inhibitor resistance mutations while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR of more than one family decreased. The overall prevalence of non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study period (p=0.01). B/F recombinants, B/G recombinants and subtype F emerged in the last period. We also noticed an increase in the number of immigrant patients (p=0.052). The proportion of men-who-have-sex-with-men (MSM) among patients with acute/recent HIV-1 infection increased over the time (p=0.04). CONCLUSIONS: The overall prevalence of TDR in patients with acute/recent HIV-1 infection in Barcelona was 9%, and it has stayed relatively stable in recent years. Non-B subtypes and immigrants proportions progressively increased.

Transmission of HIV drug resistance and non-B subtype distribution in the Spanish cohort of antiretroviral treatment naïve HIV-infected individuals (CoRIS).

CoRIS is an open multicentre cohort of HIV seroprevalent ARV-naïve subjects who began treatment at 32 Spanish healthcare centres from January 2004. Up to November 2008, a total of 683 FASTA format sequences, encoding the HIV protease and reverse transcriptase (RT) derived from plasma samples at entry into the cohort, had been obtained for examination of transmitted drug resistance (TDR) and HIV clade. TDR was found in 8.5% of the patients (4.4% NRTIs, 4% NNRTIs, 2.2% PIs). The most prevalent resistance mutations were: T215 revertants (3.8%), D67NG (1.3%), K219QENR (1.2%) and M41L (1%), for NRTIs; K103N (3.2%), for NNRTIs; I54VLMSAT, M46I and L90M (0.7%), for PIs. Non-B subtypes were recognized in 104 patients (15.2%) and were more common in Sub-Saharan Africans (15/17, 88.2%), Eastern Europeans (7/12, 58.3%) and Northern Africans (8/16, 50%) than among Spaniards (53/479, 11%) (p<0.001). The most prevalent non-B subtype was CRF02_AG (4.4%), followed by subtype D (1.9%), CRF03_AB (1.5%), CRF07_BC and subtype F1 (1%). A trend was observed for the transmission of non-B subtypes to increase and for TDR to decrease.

The natural history of liver cirrhosis in HIV-hepatitis C virus-coinfected patients.

OBJECTIVE: To provide detailed information about the natural history of HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis. METHODS: Prospective cohort including 340 HIV-HCV-coinfected patients with compensated (n = 248) or decompensated (n = 92) cirrhosis. We evaluated predictors of survival and of first hepatic decompensation. RESULTS: The mortality rate for patients with decompensated and compensated cirrhosis was 27.14 deaths per 100 person-years [95% confidence interval (CI) 18.93-35.35] and 3.98 deaths per 100 person-years (95% CI 2.42-5.54), respectively. Rate of first hepatic decompensation in patients with compensated cirrhosis was 4.62 per 100 persons-years (95% CI 2.91-6.33). In the complete cohort, permanent HAART interruption during follow-up, CD4 cell count nadir and baseline Child-Pugh score (CPS) B or C were significantly associated with shorter survival. In patients with compensated cirrhosis factors significantly associated with decreased survival were having the first hepatic decompensation during follow-up, permanent HAART discontinuation, and CPS B and C at baseline. For patients with compensated cirrhosis, time since diagnosis of HCV infection, CPS B and C and permanent HAART discontinuation were significantly associated with the risk of first hepatic decompensation. Sustained viral response to anti-HCV therapy was not independently associated with better survival in patients with compensated cirrhosis. CONCLUSION: HIV-HCV-coinfected patients with cirrhosis have a relatively good 3-year survival (87%). In contrast, 2-year survival of patients with decompensated liver cirrhosis is only 50%. Three-year survival was mostly impacted by liver-related factors and HAART maintenance.

Renal transplantation in HIV-infected patients: 2010 update.

The prognosis of human immunodeficiency virus (HIV) infection has improved in recent years with the introduction of antiretroviral treatment. While the frequency of AIDS-defining events has decreased as a cause of death, mortality from non-AIDS-related events including end-stage renal diseases has increased. The etiology of chronic kidney disease is multifactorial: immune-mediated glomerulonephritis, HIV-associated nephropathy, thrombotic microangiopathies, and so on. HIV infection is no longer a contraindication to transplantation and is becoming standard therapy in most developed countries. The HIV criteria used to select patients for renal transplantation are similar in Europe and North America. Current criteria state that prior opportunistic infections are not a strict exclusion criterion, but patients must have a CD4+ count above 200 cells/mm(3) and a HIV-1 RNA viral load suppressible with treatment. In recent years, more than 200 renal transplants have been performed in HIV-infected patients worldwide, and mid-term patient and graft survival rates have been similar to that of HIV-negative patients. The main issues in post-transplant period are pharmacokinetic interactions between antiretrovirals and immunosuppressants, a high rate of acute rejection, the management of hepatitis C virus coinfection, and the high cardiovascular risk after transplantation. More studies are needed to determine the most appropriate antiretroviral and immunosuppressive regimens and the long-term outcome of HIV infection and kidney graft.

Physicians' impression on the elders' functionality influences decision making for emergency care.

BACKGROUND AND AIMS: This study analyzes the elements that compose the emergency physicians' criterion for selecting elderly patients for intensive care treatment. This issue has not been studied in-depth. METHODS: A cross-sectional study was conducted at 4 university teaching hospitals, covering 101 randomly selected elderly patients admitted to emergency department and their respective physicians. Physicians were asked to forecast their plans for treatment or therapeutic abstention, in the event that patients might require aggressive measures (cardiopulmonary resuscitation or admission to critical care units). Data were collected on physicians' reasons for taking such decisions and their patients' functional capacity and cognitive status (Katz index and Informant Questionnaire on Cognitive Decline in the Elderly). A logistic regression model was constructed taking physicians' decisions as the dependent variables and adjusting for patient factors and physician impressions. RESULTS: The functional status reported by reliable informants and the mental status measured by validated instruments were not coincident with the physicians' perception (functional status κ, 0.47; mental status κ, 0.26). A multivariate analysis showed that the age and the functional and mental status of patients, as perceived by the physicians, were the variables that better explained the physicians' decisions. CONCLUSIONS: Physicians' impressions on the functional and mental status of their patients significantly influenced their selection of patients for high-intensity treatments despite the fact that some of these impressions were not correct.

Evaluación cognitiva de los pacientes ancianos en el servicio de urgencias: Comparación entre instrumentos estándar, historia clínica y la percepción de los médicos / Cognitive assessment of elderly patients in the emergency department: A comparison between standard tools, medical records and physicians' perception

Introducción. Hemos evaluado la exactitud con la que los médicos juzgan la capacidad cognitiva de los pacientes ancianos en el servicio de urgencias. En particular hemos evaluado la validez de la impresión subjetiva que el médico tiene sobre la cognición de sus pacientes (comparando su juicio clínico con el resultado del S-IQCODE, un test de cribado de deterioro cognitivo) y la validez de los datos de la historia clínica (comparando la información cognitiva contenida en la historia con el resultado del S-IQCODE). Material y métodos. Estudio transversal sobre 101 pacientes ancianos seleccionados al azar de entre aquellos que acudieron al servicio de urgencias, sus médicos y sus familiares-informadores. El estudio se llevó a cabo en 4 grandes hospitales universitarios entre julio y noviembre de 2003. El antecedente de deterioro cognitivo recogido en la historia fue comparado con el resultado del S-IQCODE, mediante el índice de concordancia Kappa (k). Además la impresión que los médicos pudieran tener sobre la presencia de deterioro cognitivo en sus pacientes, también fue comparada con el S-IQCODE usando el coeficiente de concordancia k. Cada paciente y su informador fueron emparejados con un solo médico. Se realizó un análisis multivariado para detectar factores asociados a la impresión del médico sobre la cognición de su paciente. Resultados. La concordancia entre la información sobre deterioro cognitivo contenida en la historia y los resultados del S-IQCODE fue de 0,47 (IC95%: 0,05–0,88). La concordancia entre la opinión del médico y el S-IQCODE fue de 0,26 (IC95%: 0,06–0,45). El análisis multivariado mostró que la impresión que el médico tenía de la situación cognitiva del paciente, estaba ligada a la impresión del médico sobre la situación funcional de su paciente, más que a ningún otro factor relacionado con la salud del paciente. Conclusiones. La situación cognitiva de los pacientes ancianos no es bien evaluada por los médicos del servicio de urgencias(AU)

Introduction. We evaluated the accuracy of physician recognition of cognitive impairment in elderly patients in emergency departments (ED). In particular, we evaluated the accuracy of the subjective impression of the physician on patients' cognition (a comparison of the information obtained from the responsible physician with the S-IQCODE, a cognitive impairment screening test), and the accuracy of the medical records (a comparison of the information in the medical record with the S-IQCODE). Material and methods. Cross-sectional study on 101 elderly patients selected at random from those attending ED, their ED physicians, and family member-carer. The study was conducted in the ED of four tertiary university teaching hospitals in a city, from July through November 2003. Cognitive data shown in the patient's medical records were compared against the S-IQCODE obtained from the family member-carer, using the kappa (k) concordance index. The physicians’ impressions on the patients’ cognitive status were also compared against the S-IQCODE results, using the kappa (k) concordance index. Each patient and their family member-carer were paired with a single physician. A logistic regression model was constructed to identify factors associated with the physicians’ impressions of the patients’ cognitive capacity. Results. The concordance between information on cognitive decline from medical records and the results of the S-IQCODE, was 0.47 (IC95%: 0.05–0.88). Concordance between the physicians’ impression on the presence of cognitive impairment, and the S-IQCODE obtained from family member-carer was 0.26 (IC95% 0.06–0.45). The multivariate analysis demonstrated that the functional status of patients, as perceived by the physicians, were the variable that better explained the physicians’ impressions of patient cognitive function. Conclusions. The cognitive status of elderly patients is not properly assessed by emergency department physicians(AU)

[Cognitive assessment of elderly patients in the emergency department: a comparison between standard tools, medical records and physicians' perception]. / Evaluación cognitiva de los pacientes ancianos en el servicio de urgencias: comparación entre instrumentos estándar, historia clínica y la percepción de los médicos.

INTRODUCTION: We evaluated the accuracy of physician recognition of cognitive impairment in elderly patients in emergency departments (ED). In particular, we evaluated the accuracy of the subjective impression of the physician on patients' cognition (a comparison of the information obtained from the responsible physician with the S-IQCODE, a cognitive impairment screening test), and the accuracy of the medical records (a comparison of the information in the medical record with the S-IQCODE). MATERIAL AND METHODS: Cross-sectional study on 101 elderly patients selected at random from those attending ED, their ED physicians, and family member-carer. The study was conducted in the ED of four tertiary university teaching hospitals in a city, from July through November 2003. Cognitive data shown in the patient's medical records were compared against the S-IQCODE obtained from the family member-carer, using the kappa (kappa) concordance index. The physicians' impressions on the patients' cognitive status were also compared against the S-IQCODE results, using the kappa (kappa) concordance index. Each patient and their family member-carer were paired with a single physician. A logistic regression model was constructed to identify factors associated with the physicians' impressions of the patients' cognitive capacity. RESULTS: The concordance between information on cognitive decline from medical records and the results of the S-IQCODE, was 0.47 (IC95%: 0.05-0.88). Concordance between the physicians' impression on the presence of cognitive impairment, and the S-IQCODE obtained from family member-carer was 0.26 (IC95% 0.06-0.45). The multivariate analysis demonstrated that the functional status of patients, as perceived by the physicians, were the variable that better explained the physicians' impressions of patient cognitive function. CONCLUSIONS: The cognitive status of elderly patients is not properly assessed by emergency department physicians.

[Factors associated with hepatic steatosis in human immunodeficiency virus and hepatits C virus coinfected patients]. / Factores asociados con esteatosis hepática en pacientes coinfectados por los virus de la inmunodeficiencia humana y de la hepatitis C.

BACKGROUND AND OBJECTIVE: To determinate the prevalence and factors associated with hepatic steatosis and severity of steatosis in human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfected patients. PATIENTS AND METHOD: Liver histology was assessed in 163 HIV-HCV coinfected patients. Exclusion criteria included positive hepatitis B surface antigen and prior anti-HCV therapy. Steatosis was scored by a single pathologist according to the percentage of affected hepatocytes. Necroinflammatory activity and fibrosis was scored by the Scheuer system. Logistic regression analyses were used to evaluate variables associated with hepatic steatosis. RESULTS: Steatosis was present in 65% of biopsy samples. Moderate-severe steatosis (>30% of hepatocytes) was detected in 17% of patients. 78.5% of patients were under high active antiretroviral therapy at the time of biopsy. In a multivariate analysis, steatosis was associated with body weight, alcohol, advanced fibrosis, stavudine use and non-use of lopinavir/ritonavir. In a multivariate analysis, severity of steatosis (>30% of hepatocytes) was associated with alcohol, HCV genotype 3, HCV load >1,400,000 copies/ml and advanced fibrosis. CONCLUSIONS: The presence of hepatic steatosis and severity of steatosis were associated with advanced fibrosis in patients coinfected with HIV and HCV. Body weight, consumption of alcohol and antiretroviral therapy (stavudine use and absence of exposure to lopinavir/ritonavir) were modifiable factors associated with the presence of steatosis. Characteristics of HCV infection were associated with the severity of steatosis in this population.

Factores asociados con esteatosis hepática en pacientes coinfectados por los virus de la inmunodeficiencia humana y de la hepatitis C / Factors associated with hepatic steatosis in human immunodeficiency virus and hepatits C virus coinfected patients

Fundamento y objetivo: determinar la prevalencia y los factores asociados con la presencia de esteatosis hepática y con su intensidad en los pacientes coinfectados por los virus de la inmunodeficiencia humana (VIH) y de la hepatitis C (VHC).Pacientes y método: se han evaluado las biopsias hepáticas de 163 pacientes coinfectados por el VIH y VHC. Se excluyó a aquéllos con antígeno de superficie del virus de la hepatitis B y tratamiento previo del VHC. El grado de esteatosis se evaluó según el porcentaje de hepatocitos afectados. La actividad necroinflamatoria y el grado de fibrosis se clasificaron según el sistema de Scheuer. Mediante regresión logística se valoraron los factores asociados con la presencia e intensidad de la esteatosis en la biopsia. Resultados: un 65% de las biopsias presentaba esteatosis, que era moderada-intensa (>30% de los hepatocitos) en un 17%. Un 78,5% de los pacientes recibía tratamiento antirretroviral de gran actividad en el momento de realizar la biopsia. Los factores asociados con la presencia de esteatosis fueron: el peso corporal, el consumo de alcohol, la presencia de fibrosis avanzada, la exposición a estavudina y la ausencia de exposición a lopinavir/ritonavir. Los factores asociados con la intensidad de la esteatosis (>30% de hepatocitos) fueron: el consumo de alcohol, el genotipo 3 del VHC, la carga vírica del VHC mayor de 1.400.000 copias de ARN/ml y la presencia de fibrosis avanzada. Conclusiones: la presencia de esteatosis y su intensidad se asociaron a un mayor grado de fibrosis hepática en los pacientes coinfectados por el VIH y VHC. El peso, el consumo de alcohol y el tratamiento antirretroviral (tratamiento con estavudina y ausencia de tratamiento con lopinavir/ritonavir) son factores modificables que se asociaron a la presencia de esteatosis. Las características de la infección del VHC estaban asociadas a la intensidad de la esteatosis en esta población (AU)

Background and objective: To determinate the prevalence and factors associated with hepatic steatosis and severity of steatos is in human immunodeficiency virus (HIV) and hepatits C virus (HCV) coinfected patients. Patients and method: Liver histology was assessed in 163 HIV-HCV coinfected patients. Exclusion criteria included positive hepatitis B surface antigen and prior anti-HCV therapy. Steatosis was scored by a single pathologist according to the percentage of affected hepatocytes. Necroinflammatory activity and fibrosis was scored by the Scheuer system. Logistic regression analyses were used to evaluate variables associated with hepatic steatosis. Results: Steatosis was present in 65% of biopsy samples. Moderate-severe steatosis (>30% of hepatocytes) was detected in 17% of patients. 78.5% of patients were under high active antiretroviral therapy at the time of biopsy. In a multivariate analysis, steatosis was associated with body weight, alcohol, advanced fibrosis, stavudine use and non-use of lopinavir/ritonavir. In a multivariate analysis, severity of steatosis (>30% of hepatocytes) was associated with alcohol, HCV genotype 3, HCV load >1,400,000 copies/ml and advanced fibrosis. Conclusions: The presence of hepatic steatosis and severity of steatosis were associated with advanced fibrosis in patients coinfected with HIV and HCV. Body weight, consumption of alcohol and antiretroviral therapy (stavudine use and absence of exposure to lopinavir/ritonavir) were modifiable factors associated with the presence of steatosis. Characteristics of HCV infection were associated with the severity of steatosis in this population (AU)

Tissue homeostasis and cancer.

Epithelial cells are known to release an important amount of cytokines capable to modulate immune system functions. On the other hand, immune system cells can release cytokines, which play an important role in the control of the growth of epithelial cells. In this paper, we stand the hypothesis that a mutual (reciprocal) growth regulation exists between epithelial cells and immune system. We propose a model describing plausible cytokine circuits that may regulate (inhibit) both epithelial growth and epithelial inflammation. In addition, we describe how dysfunction of these circuits could lead to tumoral growth, excessive inflammation or both. A failure in the regulation of epithelial growth by the immune system could give rise to a neoplasm, and a failure in the regulation of the immune system by the epithelium could give rise to inflammatory or autoimmune diseases. This model may satisfactorily explain the link between inflammation and cancer.

Functional assessment of older patients in the emergency department: comparison between standard instruments, medical records and physicians' perceptions.

BACKGROUND: We evaluated the accuracy of physician recognition of functional status impairment in older emergency departments (ED) patients. In particular, we evaluated the accuracy of medical records (a comparison of the information in the medical record with the functional status based on proxy interviews), and the accuracy of physician knowledge (a comparison of the information obtained from the responsible physician with the functional status based on proxy interviews). METHODS: Cross-sectional study on 101 frail older patients selected at random from among those attending ED, their ED physicians, and respondents. The study was conducted at ED in four general university teaching hospitals in a city, from July through November 2003. Functional data shown on patients' medical records were compared against functional data obtained from respondents (family members), using Kendall's Tau-b statistic. In addition patients' Katz Indices (which assesses six basic activities of daily living--basic ADL) based on interviews with ED physicians were compared against those obtained from respondents, using the coefficient of concordance weighted kappa (kappa). Each patient and his respondent were paired with a single physician. RESULTS: The correlation between information on dependence for basic ADL obtained from medical records and that furnished by respondents, was 0.41 (95% CI 0.27-0.55). Concordance between the respective Katz Indices obtained from physicians and respondents was 0.47 (95% CI 0.38-0.57). CONCLUSION: Older subjects' functional status is not properly assessed by emergency department physicians.