785 research outputs found
Inclusive healthcare in light of the new MASLD guidelines: Should people living with HIV be screened for liver fibrosis?
No full textHyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients
No full textBackground: Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study.
Methods: Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls).
Results: During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001).
Conclusions: An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications
The use of intrahepatic portosystemic shunt in HIV positive patients: A retrospective multicentric study
No full textThe use of intrahepatic portosystemic shunt in HIV positive patients: A retrospective multicentric study
No full textRegaining Motor Control in Musician's Dystonia by Restoring Sensorimotor Organization
No full textProfessional musicians are an excellent human model of long term effects of skilled motor training on the structure and function of the motor system. However, such effects are accompanied by an increased risk of developing motor abnormalities, in particular musician's dystonia. Previously we found that there was an expanded spatial integration of proprioceptive input into the hand area of motor cortex (sensorimotor organisation, SMO) in healthy musicians as tested with a transcranial magnetic stimulation (TMS) paradigm. In musician's dystonia, this expansion was even larger, resulting in a complete lack of somatotopic organisation. We hypothesised that the disordered motor control in musician's dystonia is a consequence of the disordered SMO.
In the present paper we test this idea by giving pianists with musician's dystonia 15 min experience of a modified proprioceptive training task. This restored SMO towards that seen in healthy pianists. Crucially, motor control of the affected task improved significantly and objectively as measured with a MIDI piano, and the amount of behavioural improvement was significantly correlated to the degree of sensorimotor re-organisation. In healthy pianists and non-musicians, the SMO and motor performance remained essentially unchanged. These findings suggest a link between the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks in highly skilled individuals
Patientenkollektiv einer HIV-Schwerpunktpraxis
No full textIn der vorliegenden Arbeit wurden retrospektiv die 192 HIV-positiven Patienten des Jahres 2005 mit follow-up bis Ende 2006 der Praxis Dr. med. K. Isernhagen und Dr. med. K. Römer in Köln untersucht. Die Daten der Patienten wurden nach epidemiologischen, klinischen und laborchemischen Aspekten ausgewertet. Die Geschlechtsverteilung lag bei 65% männlichen und 35% weiblichen Patienten. Die Mehrzahl der Patienten stammte aus Deutschland. Der relevante Risikofaktor für die HIVInfektion lag bei weiblichen Patienten in der Herkunft aus einem Endemiegebiet. Bei den männlichen Patienten lag ungeschützter homo- oder bisexueller Geschlechtsverkehr an erster Stelle. Die Patienten waren bei Erstvorstellung im Jahr 2005 zwischen 18 und 71 Jahren alt. Das mediane Lebensalters bei lag bei 39 Jahren. Bei der Mehrzahl der Patienten wurde die HIV-Infektion erstmalig in den 90erJahren diagnostiziert. Es finden sich von 1993 bis 2000 zunehmend weibliche Patienten mit HIV-Neuinfektion. Die Patienten waren bei HIVErstdiagnose im Median 30 Jahre alt. Bei Beginn und am Ende des Beobachtungszeitraumes befand sich die Mehrzahl der Patienten im CDC-Stadium A (42% bzw. 38%). 5% der Patienten erkrankte während des Beobachtungszeitraumes neu an AIDS. Die Mehrzahl der Patienten erhielt bei Erstvorstellung im Jahr 2005 bereits eine antiretrovirale Therapie. 9% der Patienten erhielt erstmalig eine antiretrovirale Therapie mit 100%igem immunologischen und 65%igem virologischen Therapieerfolg. Die häufigste Medikamentenkombination bestand aus zwei NRTI mit einem PI. Das Therapieregime wurde bei weiblichen Patienten deutlich häufiger umgestellt als bei männlichen Patienten. 7 Schwangerschaften wurden ausgetragen. Am Ende des Beobachtungszeitraumes waren noch 16% der Patienten therapienaiv. 4% nahmen keine antiretrovirale Therapie. Insgesamt 4% der Patienten verstarben während des Beobachtungszeitraumes. Kein Patient verstarb während des Beobachtungszeitraumes an einer AIDS-definierenden Erkrankung
Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time
No full textThe introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright © 2016 John Wiley & Sons, Ltd
European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults.
No full textOBJECTIVES: With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted. SUMMARY: Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy. With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50\% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present. CONCLUSIONS: Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality
Cellular stress triggers the human topoisomerase I damage response independently of DNA damage in a p53 controlled manner
No full textThe 'human topoisomerase I (htopoI) damage response' was reported to be triggered by various kinds of DNA lesions. Also, a high and persistent level of htopoI cleavage complexes correlated with apoptosis. In the present study, we demonstrate that DNA damage-independent induction of cell death using colcemid and tumor necrosis factor alpha is also accompanied by a strong htopoI response that correlates with the onset of apoptotic hallmarks. Consequently, these results suggest that htopoI cleavage complex formation may be caused by signaling pathways independent of the kind of cellular stress. Thus, protein interactions or signaling cascades induced by DNA damage or cellular stress might lead to the formation of stabilized cleavage complexes rather than the DNA lesion itself. Finally, we show that p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid.No Full Tex
The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women
No full textContains fulltext :
117827.pdf (Publisher’s version ) (Closed access)OBJECTIVE:: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum. DESIGN:: A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. METHODS:: HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. Twenty-four-hour pharmacokinetic curves were recorded in the third trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0. RESULTS:: Thirty-four women were included in the analysis. Geometric mean ratios of third trimester vs. postpartum [90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area under the curve (AUC0-24 h); 0.81 (0.68-0.96) for TDF Cmax and 0.79 (0.70-0.90) for TDF C24 h and 0.75 (0.68-0.82) for FTC AUC0-24 h; and 0.87 (0.77-0.99) for FTC Cmax and 0.77 (0.52-1.12) for FTC C24 h. The viral load close to delivery was less than 200 copies/ml in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported. CONCLUSION:: Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother-to-child transmission
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