In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease ...inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.
In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ≥ 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.
Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15).
Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. Methods. We prospectively included ...aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. Results. Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was −0.04 (95% confidence interval, −.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, −0.09 95% confidence interval, −.16 to −.01 vs −0.08 −.14 to −.02, after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 22.2%; triple therapy, 4 of 19 21.1%; P = .91) and vice versa (monotherapy, 5 of 44 10.2% and triple therapy, 3 of 45 6.3%; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. Conclusions. The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.
Background & Aims
Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with ...Child‐Turcotte‐Pugh (CTP) score and hepatic decompensation in HIV/HCV‐coinfected and HCV‐monoinfected patients with advanced cirrhosis.
Methods
A cross‐sectional study was carried out in 62 HIV/HCV‐coinfected and 28 HCV‐monoinfected patients. Metabolomics analysis was performed by gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐mass spectrometry (LC‐MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS‐DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score).
Results
The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy‐related metabolites and bacterial fermentation‐related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched‐chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV‐ and HCV‐infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7).
Conclusion
Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV‐coinfected and HCV‐monoinfected patients.
Abstract Objective To evaluate the effect on creatinine clearance (CG-CrCl, Cockcroft–Gault equation) of switching to boosted protease inhibitor (PI) monotherapy in patients receiving a triple drug ...antiretroviral regimen containing TDF. Methods All patients who had received a TDF-containing regimen for at least one year and had been switched to PI monotherapy were included. A rapid decrease in CG-CrCl during exposure to TDF was defined as a decrease in CG-CrCl at least five times higher than the expected due to age (0.4 ml/min/year by the years of exposure to TDF). In this subgroup of patients, we considered improvement if the last value of CG-CrCl on PI monotherapy was 10% higher than the last value of CG-CrCl before switching to PI monotherapy. A multivariate logistic regression was constructed to identify factors associated to renal improvement after switching to bPI monotherapy. Results 64 patients included. The median (IQR) annual change in CG-CrCl during PI monotherapy was significantly lower than the median (IQR) annual change while exposed to TDF −0.9 (−4.7 to +2.8) ml/min vs. −4 (−8 to −1) ml/min, p = 0.001. 44 patients experienced a rapid decline during TDF exposition. After switch to PI monotherapy, 15/44 (34%, 95% CI: 21–50%) had an improved CG-CrCl and 16/44 (36%, CI 23–52%) experienced a further decline in CG-CrCl. The only variable associated to CG-CrCl improvement was a more rapid CG-CrCl decline in the last year of exposure to TDF. Conclusion Switching to PI monotherapy partially reversed CG-CrCl decrease associated to TDF use, especially in patients with a more rapid decline while receiving TDF.
Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic.
The objective of the study to describe the ...clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC).
We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020.
We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m
and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died.
Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.
It is recommended that patients with cirrhosis undergo endoscopic screening to rule out the presence of gastroesophageal varices: a noninvasive predictive method to identify cirrhotic patients with a ...very low risk of esophageal varices could potentially avoid unnecessary endoscopies.
We studied in 85 HIV-infected patients with cirrhosis the association between the absence of esophageal varices and portal hypertensive gastropathy, assessed by endoscopy, and liver stiffness measurement by transient elastography. We analyzed other parameters related to portal hypertension and hepatic function.
Values of transient elastography and platelet count were significantly associated with absence of esophageal varices/portal hypertensive gastropathy. The area under the receiver operating characteristics curve 95% confidence interval (CI) of transient elastography for the prediction of the absence of esophageal varices/portal hypertensive gastropathy was 0.7 (0.58-0.81). A liver stiffness measurement value less than 20 kPa was highly predictive of the absence of esophageal varices and portal hypertensive gastropathy. The combination of transient elastography (<20 kPa) and platelet count (>120 × 10 cells/l) had the highest negative predictive value (100%, CI 95% 77.2-100) for absence of esophageal varices and portal hypertensive gastropathy.
Transient elastography combined with platelet count is useful for predicting the absence of esophageal varices and portal hypertensive gastropathy and, therefore, avoid unnecessary diagnostic endoscopies in HIV-infected patients with liver cirrhosis.
Summary
We conducted a phase 2 trial to evaluate the safety and efficacy of bendamustine instead of BCNU (carmustine) in the BEAM (BCNU, etoposide, cytarabine and melphalan) regimen (BendaEAM) as ...conditioning for autologous stem‐cell transplantation (ASCT) in patients with aggressive lymphomas. The primary endpoint was 3‐year progression‐free survival (PFS). Sixty patients (median age 55 28–71 years) were included. All patients (except one who died early) engrafted after a median of 11 (9–72) and 14 (4–53) days to achieve neutrophil and platelet counts of >0.5 × 109/l and >20 × 109/l, respectively. Non‐relapse mortality at 100 days and 1 year were 3.3% and 6.7%, respectively. With a median follow‐up of 67 (40–77) months, the estimated 3‐year PFS and overall survival (OS) were 58% and 75%, respectively. Patients in partial response at study entry had significantly worse PFS and OS than patients who underwent ASCT in complete metabolic remission, and this was the only prognostic factor associated with both PFS (Relative risk RR, 0.27 95% confidence interval {CI} 0.12–0.56) and OS (RR, 0.40 95% CI 0.17–0.97) in the multivariate analysis. BendaEAM conditioning is therefore a feasible and effective regimen in patients with aggressive lymphomas. However, patients not in complete metabolic remission at the time of transplant had poorer survival and so should be considered for alternative treatment strategies.
Objectives Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk ...of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development. Methods A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. Results Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007). Discussion CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Six carbon materials were obtained from the carbonisation of resorcinol/formaldehyde xerogels. All carbon xerogels (CXs) showed essentially the same microporosity but differed in their meso- or ...macroporosity, covering a wide interval of average meso- or macropore sizes from 10 nm to 3000 nm. The graphitisation of the CXs was heterogeneous, as detected by X-ray diffraction. The relative amount of the amorphous, turbostratic and graphitic carbon phases on the graphitised xerogels was different depending on the pore size of the CXs. Crystalline parameters such as interlayer spacings (d002) and crystallite sizes along the c-axis (Lc) were calculated from the different contributions and were also found to depend on the pore size of the parent CXs. Transmission electron microscopy and Raman spectroscopy analyses helped to identify nanostructures that could be assigned to the three carbon components of the graphitic xerogels. The occurrence of most of these nanostructures was compatible with a solid-phase transformation of the amorphous precursor. The electrical conductivity of the graphitised xerogels also depended on their original pore size, with values ranging from 2 S cm−1 for the materials with a 10 nm pore size to 18 S cm−1 for the materials with bigger pore sizes.
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