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Early systemic and central nervous system viral replication and inflammation may impact brain integrity in people with HIV (PWH), leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART.
HIV-infected MSM and transgender women (average age 27 and education 13 years) enrolled within 100 days from estimated date of detectable infection [EDDI]. A cognitive performance (NP) protocol was administered at enrollment (before ART initiation) and every 24 weeks until week 192. An overall index of cognitive performance (NPZ) was created using local normative data. Blood (n=87) and cerebrospinal fluid (CSF; n=29) biomarkers of inflammation and neuronal injury were examined before ART initiation. Regression analyses assessed relationships between time since EDDI, pre-ART biomarkers, and NPZ.
Adjusting for multiple comparisons, shorter time since EDDI wapairment.
HIV and pregnancy may affect latent TB infection (LTBI) diagnostics. Tuberculin skin test (TST) and newer generation QuantiFERON-TB Gold Plus (QFT-Plus) evaluations in pregnant women with (WLHIV) and without HIV are lacking.
In this cross-sectional study, pregnant women underwent TST and QFT-Plus testing during antenatal care in Kenya. We estimated LTBI prevalence and TST and QFT-Plus performance. Diagnostic agreement was assessed with kappa statistic, participant characteristics associated with LTBI and HIV with generalized linear models, and QFT-Plus quantitative responses with Mann Whitney test.
We enrolled 400 pregnant women (200 WLHIV/200 HIV-negative) at median 28 weeks gestation (Interquartile Range [IQR] 24-30). Among WLHIV (all on antiretroviral therapy), median CD4 was 464 cells/mm3 (IQR 325-654); 62.5% (125) had received isoniazid preventive therapy. LTBI prevalence was 35.8% and similar among WLHIV and HIV-negative women. QFT-Plus identified 3-fold more women with LTBI vs. TST (32% vs. 12%, revention studies which rely on these diagnostics for TB-infection entry criteria or outcomes.
A knowledge gap exists for dolutegravir (DTG) pharmacokinetics and safety during the first 4 weeks of life, preventing safe and effective DTG use in neonates.
Population pharmacokinetic (popPK) modeling and simulation was used to assess newborn DTG dosing requirements during the first days of life as a function of maternal DTG dosing history prior to delivery.
DTG PK data were obtained from pregnant women and infants enrolled in the IMPAACT Network P1026S study. Maternal and neonate popPK models were separately developed. Monte Carlo simulations were performed to simulate neonatal concentrations following two doses of DTG after birth for infants born to mothers either receiving or not receiving DTG prior to delivery.
In DTG-naïve infants, a 5 mg DTG dose at birth with a second dose after 48 hours maintained median concentrations above the lower bound of the target range (0.77 μg/mL) and below the upper bound of the target range (7.34 μg/mL representing 2-fold above the adult Cmax value). In DTG-exposed infants, a 5 mg DTG dose at 24 hours after birth with a second dose after 48 hours maintained median concentrations within or nearly within the target range, even if the last maternal DTG dose was taken as soon as 6 hours or as long as 24 hours prior to delivery.
Newborn DTG dosing requirements during the first days of life depend upon maternal DTG dosing history prior to delivery. These results may inform the design of future clinical studies of DTG in the neonatal population.
Newborn DTG dosing requirements during the first days of life depend upon maternal DTG dosing history prior to delivery. These results may inform the design of future clinical studies of DTG in the neonatal population.
Brain derived neurotrophic factor (BDNF) shows consistent associations with memory across many clinical populations, including dementia. Less is understood about the association between BDNF and memory functioning in people living with HIV (PWH).
A sample of 173 adults aged 50+ (n=100 HIV+ and n=73 HIV seronegative) completed a comprehensive neurobehavioral assessment and blood draw. Linear regressions predicting memory domains (learning, delayed recall, recognition) were conducted including race (White vs. Black/African American), HIV status, BDNF, and their interactions.
For learning and delayed recall, significant (p<0.05) main effects for race and interactions for BDNF x race and HIV status x race were found, while for recognition, only a BDNF x race interaction emerged. In adjusted models, BDNF x race interactions remained for learning and delayed recall. Brr2 Inhibitor C9 datasheet To determine effect size, correlations were conducted between BDNF and memory domains stratified by HIV serostatus and race, and small-medium needed to replicate findings, and determine mechanisms for racial differences in BDNF associations with memory.
Optic neuropathy in the context of leukemia and lymphoma raises concern for central nervous system involvement or relapse and warrants prompt evaluation and treatment. To date, a gold standard for the diagnosis and management of leukemic optic neuropathy has yet to be established.
Case series and review of the literature. Two illustrative cases were selected to discuss their treatment course and outcome.
We report 7 cases of patients with leukemia or lymphoma presenting with optic nerve infiltration. All patients received steroid therapy for presumed infiltrative optic neuropathy, and 4 patients underwent radiation therapy. Along with systemic chemotherapy, all patients received intrathecal chemotherapy except one. Three patients received chimeric antigen receptor T-cell therapy.
Leukemic and lymphomatous optic neuropathy is difficult to diagnose and treat, and there is no gold standard for diagnosis or treatment in the current literature. We help clarify how this disease should be approached in a multidisciplinary fashion and on an individual basis to correctly diagnose and treat the vision loss, while considering the patient's long-term prognosis based on their systemic disease.
Leukemic and lymphomatous optic neuropathy is difficult to diagnose and treat, and there is no gold standard for diagnosis or treatment in the current literature. We help clarify how this disease should be approached in a multidisciplinary fashion and on an individual basis to correctly diagnose and treat the vision loss, while considering the patient's long-term prognosis based on their systemic disease.
In this study we evaluate the diagnostic accuracy of extraocular muscle volumetry in detecting thyroid eye disease and to compare the results with simple measurements of maximal medial rectus (MR) diameter.
Cross-sectional study that included 47 eyes of 47 patients with thyroid eye disease and 47 healthy controls. Patients underwent slitlamp examination and imaging consisting of computed tomography scans. Image segmentation and volume measurements were performed by 2 independent researchers. Intraobserver and interobserver reliability testing was also conducted.
Total extraocular muscle volume was 7.31 ± 1.88 cm3 and medial volume was 2.38 ± 0.73 cm3 in the study group. In this group, the maximum measured diameter of the MR was 6.67 ± 0.35 mm. MR volume was statistically associated with maximum MR diameter (r = 9.78; P < 0.001). Both MR volume and maximum MR diameter measurements showed good predictive efficacy as shown using receiver operator characteristic curve analysis.
Complications of thyroid eye disease are often sight threatening, and timely diagnosis is crucial for the management of the entity and its sequelae. The results of this study imply that simple measurements of maximum MR diameter are sensitive enough to establish diagnosis.
Complications of thyroid eye disease are often sight threatening, and timely diagnosis is crucial for the management of the entity and its sequelae. The results of this study imply that simple measurements of maximum MR diameter are sensitive enough to establish diagnosis.
Syphilis is an uncommon cause of optic nerve head edema; however, differentiating syphilis from other etiologies of optic nerve head swelling may be challenging. We describe 4 cases of ocular syphilis presenting with swollen optic nerve head(s) without overt signs of intraocular inflammation to better define the phenotypic presentation of this condition to allow its early recognition and treatment and discuss potential pathophysiological mechanisms of syphilitic optic neuropathy.
Retrospective case series of patients presenting to a tertiary neuro-ophthalmology practice with a swollen optic nerve head(s) but no overt signs of intraocular inflammation, which was eventually determined to be secondary to syphilis.
Four patients were included in the study. The mean age was 43 years, 2 were women and 2 had bilateral involvement. Two patients had a recent history of skin rash, and one patient was investigated for abdominal pain and elevated liver enzymes. Two patients presented with photopsias and preserved vhy, with its pathophysiology likely similar to meningitis seen in neurosyphilis.
Inherited optic neuropathies (IONs) cause progressive irreversible visual loss in children and young adults. There are limited disease-modifying treatments, and most patients progress to become severely visually impaired, fulfilling the legal criteria for blind registration. The seminal discovery of the technique for reprogramming somatic nondividing cells into induced pluripotent stem cells (iPSCs) has opened several exciting opportunities in the field of ION research and treatment.
A systematic review of the literature was conducted with PubMed using the following search terms autosomal dominant optic atrophy, ADOA, dominant optic atrophy, DOA, Leber hereditary optic neuropathy, LHON, optic atrophy, induced pluripotent stem cell, iPSC, iPSC derived, iPS, stem cell, retinal ganglion cell, and RGC. Clinical trials were identified on the ClinicalTrials.gov website.
This review article is focused on disease modeling and the therapeutic strategies being explored with iPSC technologies for the 2 most commonthat iPSCs offer. This fast-moving area will remain at the forefront of both basic and translational ION research in the coming years, with the potential to accelerate the development of effective therapies for patients affected with these blinding diseases.
The standard open reduction and internal fixation technique with a plate and screws for a simple midshaft clavicular fracture necessitates a relatively large incision, and can also lead to variable amount of keloid scar formation. Historically, other techniques of more minimally-invasive retrograde intramedullary fixation with the entry point posterolaterally on the shoulder have shown their own disadvantages and complications. We present a surgical technique of antegrade intramedullary fixation for midshaft clavicular fractures and an illustrative case series.
The standard open reduction and internal fixation technique with a plate and screws for a simple midshaft clavicular fracture necessitates a relatively large incision, and can also lead to variable amount of keloid scar formation. Historically, other techniques of more minimally-invasive retrograde intramedullary fixation with the entry point posterolaterally on the shoulder have shown their own disadvantages and complications. We present a surgical technique of antegrade intramedullary fixation for midshaft clavicular fractures and an illustrative case series.