Abstract
Testing and treatment of tuberculosis infection (TBI) are recommended for people living with HIV (PLWH). We aimed to evaluate the care cascade of TBI treatment among PLWH in the era of ...antiretroviral therapy (ART) scale-up. This retrospective study included adult PLWH undergoing interferon-gamma release assay (IGRA)-based TBI screening during 2019–2021. PLWH testing IGRA-positive were advised to receive directly-observed therapy for TBI after active TB disease was excluded. The care cascade was evaluated to identify barriers to TBI management. Among 7951 PLWH with a median age of 38 years and CD4 count of 616 cells/mm
3
, 420 (5.3%) tested positive and 38 (0.5%) indeterminate for IGRA. The TBI treatment initiation rate was 73.6% (309/420) and the completion rate was 91.9% (284/309). More than 80% of PLWH concurrently received short-course rifapentine-based regimens and integrase strand transfer inhibitor (InSTI)-containing ART. The main barrier to treatment initiation was physicians’ concerns and patients’ refusal (85.6%). The factors associated with treatment non-completion were older age, female, anti-HCV positivity, and higher plasma HIV RNA. Our observation of a high TBI completion rate among PLWH is mainly related to the introduction of short-course rifapentine-based regimens in the InSTI era, which can be the strategy to improve TBI treatment uptake.
Hepatitis C virus (HCV) genotype 6 (HCV-6) infection is prevalent predominantly in Southeast Asia, and the data on the virologic response of HCV-6 to direct-acting antivirals (DAAs) are sparse in ...people living with human immunodeficiency virus (HIV) (PLWH).
To assess the virologic response of HCV-6 to DAAs in PLWH.
From September 2016 to July 2019, PLWH coinfected with HCV-6 initiating DAAs were included. Laboratory investigations were performed at baseline, the end of treatment, and 12 wk off-therapy.
Of the 349 PLWH included (mean age 48.9 years, 82.5% men), 80.5% comprised people who inject drugs, 18.1% men who have sex with men, and 1.4% heterosexuals. Coexistent hepatitis B virus infection was present in 12.3% of the included PLWH, liver cirrhosis 10.9%, hepatocellular carcinoma 0.9%, and previous HCV treatment experience 10.9%. The mean baseline plasma HCV RNA was 6.2 log
IU/mL. Treatment with glecaprevir/pibrentasvir was initiated in 51.9%, sofosbuvir/ledipasvir 41.5%, sofosbuvir/velpatasvir 6.3%, and sofosbuvir/daclatasvir 0.3%. At DAA initiation, antiretroviral therapy containing tenofovir alafenamide was given in 26.4%, tenofovir disoproxil fumarate 34.4%, non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%, non-nucleoside reverse-transcriptase inhibitors 30.4%, protease inhibitors 4.0%, and integrase strand transfer inhibitors 66.8%; 94.8% of the included patients had CD4 counts ≥ 200 cells/mm
and 96.0% had plasma HIV RNA < 50 copies/mL. Overall, 96.8% achieved undetectable plasma HCV RNA (< 30 IU/mL) at end of treatment; and 92.3% achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis (93.5% in patients receiving sofosbuvir-based DAAs and 91.2% in those receiving glecaprevir/pibrentasvir).
Similar to the observation made in HIV-negative patients, sustained virologic response 12 wk off-therapy with DAAs is high in PLWH coinfected with HCV-6.
Alzheimer's disease patients are increasing rapidly every year. Scholars tend to use computer vision methods to develop automatic diagnosis system. (Background) In 2015, Gorji et al. proposed a novel ...method using pseudo Zernike moment. They tested four classifiers: learning vector quantization neural network, pattern recognition neural network trained by Levenberg-Marquardt, by resilient backpropagation, and by scaled conjugate gradient.
This study presents an improved method by introducing a relatively new classifier-linear regression classification. Our method selects one axial slice from 3D brain image, and employed pseudo Zernike moment with maximum order of 15 to extract 256 features from each image. Finally, linear regression classification was harnessed as the classifier.
The proposed approach obtains an accuracy of 97.51%, a sensitivity of 96.71%, and a specificity of 97.73%.
Our method performs better than Gorji's approach and five other state-of-the-art approaches. Therefore, it can be used to detect Alzheimer's disease.
In vivo effects of histidine and carnosine against diabetic deterioration in diabetic Balb/cA mice were studied. Histidine and carnosine at 0.5, 1 g/l were added into drinking water. After 4 weeks ...intake of these agents, the content of histidine and carnosine in plasma, heart and liver significantly elevated (
P<0.05). The intake of these agents significantly decreased plasma glucose and fibronectin levels (
P<0.05); however, only 1 g/l histidine and carnosine treatments significantly increased insulin level (
P<0.05) in diabetic mice. Triglyceride level in heart and liver was dose-dependently reduced by histidine or carnosine treatments (
P<0.05); however, only 1 g/l histidine and carnosine treatments significantly reduced cholesterol level in heart and liver (
P<0.05). The administration of histidine or carnosine significantly enhanced catalase activity and decreased lipid oxidation levels in kidney and liver (
P<0.05); however, only 1 g/l histidine and carnosine treatments significantly increased glutathione peroxidase activity (
P<0.05). The increased interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in diabetic mice were significantly suppressed by the intake of histidine or carnosine (
P<0.05). In human low density lipoprotein, histidine or carnosine showed dose-dependently suppressive effect in glucose-induced oxidation and glycation (
P<0.05). These data suggest that histidine and carnosine are potential multiple-protective agents for diabetic complications prevention or therapy.
This multicenter study aimed to evaluate the seroprevalence of hepatitis B virus (HBV) and the use of combination antiretroviral therapy (cART) among patients receiving HIV care in Taiwan.
We ...retrospectively reviewed the medical records of HIV-infected adult patients who initiated cART at 11 designated hospitals in Taiwan between 2012 and 2016. The clinical information collected included serological profiles on HBV, hepatitis C virus (HCV), and syphilis, plasma HIV RNA load, nadir CD4 cell count, and antiretrovirals with activity against both HBV and HIV (tenofovir disoproxil fumarate TDF, lamivudine LAM, and emtricitabine FTC).
We analyzed 1800 HIV-infected patients; 1742 (96.8%) were male and 794 (44.1%) were born after July, 1986, when nationwide universal neonatal HBV vaccination was implemented. HBsAg positive results were 11.6% (209/1800), which decreased significantly from 18.1% (182/1006) in those born before July 1986 to 3.4% (27/794) in those born after. In multivariable analysis, HBsAg positivity was significantly associated with age (adjusted odds ratio aOR 1.06, 95% confidence interval CI 1.05–1.08), CD4≧200 cells/μL (aOR 0.73, 95% CI 0.53–0.99), and HCV seropositivity (aOR 1.62, 95% CI 1.06–2.50). Of 209 HBV/HIV-coinfected patients, 31.1% started cART containing only LAM with anti-HBV activity, while 68.9% started cART containing TDF plus LAM or coformulated TDF/FTC.
The overall prevalence of HBV/HIV coinfection remained high among HIV-infected patients in Taiwan. Despite recommendations of the HIV treatment guidelines for the management of HBV infection, a substantial proportion of HIV/HBV-coinfected patients received cART containing only LAM for HBV infection.
This study aimed to investigate the association between herpes zoster (HZ) and human immunodeficiency virus (HIV). Data were retrieved from the Longitudinal Health Insurance Databases (LHID 2005 and ...2010), Taiwan. The International Classification of Diseases, 9th Revision, Clinical Modification ICD-9-CM codes were used to identify Hz from 2001-2004. Identification of HIV infection was from 2005-2010. The hazard ratios of HIV among herpes zoster infected and non-herpes zoster infected patients were estimated using multiple Cox proportional hazard model. In general, 19685 participants were identified with Hz. The HIV incidence rates (per 104 person-months) in herpes zoster infected and non-infected patients were 0.191(95% CI 0.130-0.280) and 0.079 (95% CI 0.074-0.084), respectively while the hazard ratio (HR) of HIV among infected individuals was 3.518 (95% CI 2.375-5.211). This study concludes that herpes zoster could be considered as a predictor of HIV infection especially among Asian populations, hence it is vital to test herpes zoster infected individuals for HIV antibodies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES:Treatment with trimethoprim-sulfamethoxazole for Pneumocystis pneumonia (PCP) is often associated with adverse effects. Echinocandins, by inhibiting the cyst form of Pneumocystis ...jirovecii, may be an alternative therapy for PCP. However, clinical experience with echinocandins in the treatment of PCP remains limited among HIV-infected patients.
METHODS:From August 2013 to April 2018, data of HIV-infected patients with confirmed PCP who received echinocandins as alternative treatment because of intolerance or unresponsiveness to trimethoprim-sulfamethoxazole were retrospectively reviewed to assess the effectiveness and safety of echinocandins alone or in combination with other agents.
RESULTS:In total, 34 patients were included, with a median CD4 count of 27 cells/μl interquartile range (IQR), 20–93). Twenty-four patients (70.6%) presented with moderate-to-severe PCP. The most common adverse effects leading to withdrawal of trimethoprim-sulfamethoxazole were hepatotoxicity (29.4%), gastrointestinal upset (23.5%), and rash (17.6%). Nine patients (26.5%) were switched to echinocandins after failure of trimethoprim-sulfamethoxazole. The median interval before switch from trimethoprim-sulfamethoxazole to echinocandins was 9.0 days (IQR 5.0–14.0). The all-cause and PCP-related in-hospital mortality rate of patients receiving echinocandins as alternative therapy was 20.6% (7/34) and 14.7% (5/34), respectively. The all-cause in-hospital mortality was 0% in mild PCP cases and 29% (7/24) in moderate-to-severe PCP cases. Patients who had failed to respond to first-line trimethoprim-sulfamethoxazole treatment tended to have a higher in-hospital mortality rate than those without first-line trimethoprim-sulfamethoxazole failure (44.4% versus 12.0%, P = 0.06).
CONCLUSION:Echinocandin therapy might serve as an alternative option for HIV-infected patients with PCP who are intolerable to trimethoprim-sulfamethoxazole.
Pyogenic liver abscess (PLA) is a major life-threatening disease with varied clinical features. This study aimed to determine predictors of mortality in patients with PLA using criteria determined ...upon admission. We retrospectively examined the data of 324 hospitalized adults in whom liver abscesses were confirmed using abdominal ultrasound and/or computed tomography. The relationship between various risk factors was assessed using multivariate analysis. A total of 109 (33.6%) patients were admitted to the intensive care unit (ICU). The overall mortality rate was 7.4% and was higher among ICU patients than non-ICU patients (21.1% vs. 0.5%, p < 0.001). PLA patients with an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥18 had a 19.31-fold increased risk, and those with concomitant infections had a 34.33-fold increased risk of 30-day mortality according to multivariate analysis. The estimated area under the receiver operating characteristic curve for predicting 30-day mortality revealed that APACHE II score ≥18 (sensitivity of 75% and specificity of 84%, p < 0.0001) had better discriminative power than Sequential Organ Failure Assessment (SOFA) ≥6 (sensitivity of 81% and specificity of 66%, p < 0.0001). APACHE II has shown better discrimination ability than SOFA in predicting mortality in PLA patients. To improve outcomes in patients with PLA, future management strategies should focus on high-risk patients.
Candida albicans (C. albicans) CDC4 (CaCDC4), encoding the F‑box protein for the substrate specificity of the Skp1‑cullin‑F‑box E3 ubiquitin ligase complex, suppresses the yeast‑to‑filament ...transition in C. albicans. In our previous study, Thr1 was identified as a CaCdc4‑associated protein using affinity purification. THR1 encodes a homoserine kinase, which is involved in the threonine biosynthesis pathway. The present study generated a strain with repressible CaCDC4 expression and continuous THR1 expression. Colony and cell morphology analyses, as well as immunoblotting, revealed that the Thr1 protein was detectable under conditions in which the expression of CaCDC4 was repressed and that the filaments resulting from the repressed expression of CaCDC4 were suppressed by the constitutive expression of THR1 in C. albicans. Additionally, by using the CaSAT1‑flipper method, the present study produced null mutants of THR1, GCN4, and CaCDC4. The phenotypic consequences were evaluated by growth curves, spotting assays, microscopic analysis, reverse transcription‑polymerase chain reaction and XTT‑based biofilm formation ability. The results revealed that fewer cells lacking THR1 entered the stationary phase but had no apparent morphological alteration. It was observed that the expression of THR1 was upregulated concurrently with GCN4 during nutrient depletion and that cells lacking GCN4 rescued the lethality of cells in the absence of THR1 in conditions accumulating homoserine in the threonine biosynthesis pathway. Of note, it was found that cells with either CaCDC4 or THR1 loss were sensitive to oxidative stress and osmotic stress, with those with THR1 loss being more sensitive. In addition, it was observed that cells with loss of either CaCDC4 or THR1 exhibited the ability to increase biofilm formation, with those lacking CaCDC4 exhibiting a greater extent of enhancement. It was concluded that CaCDC4 is important in the coordination of morphogenesis, nutrient sensing, and the stress response through THR1 in C. albicans.
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