Persistent abnormalities in lymphoid tissues of human immunodeficiency virus-infected patients successfully treated with highly active antiretroviral therapy

Effective highly active antiretroviral therapy (HAART) for human immunodeficiency virus type 1 is associated with virus suppression and immune reconstitution. However, in some patients, this reconstitution is partial or incomplete because CD4(+) cell counts do not increase significantly. This may be due to damage in the microenvironment of lymphoid tissues (LTs), where CD4(+) T cells reside. To test this hypothesis, LT samples were obtained from 23 patients enrolled in a prospective trial that compared 3 different HAART regimens. Analysis of LT architecture and CD4(+) T cells populations revealed abnormalities in 100% of the LT samples, especially in the follicles, with 43% showing absence, 14% showing regression, and 43% showing hyperplasia. CD4(+) T cell populations were abnormal in 16 (89%) of 18 tissue samples, with 7 (39%) of 18 decreased by >50% of normal levels. These data are consistent with the hypothesis that persistent abnormalities in the microenvironment can influence immune reconstitution and document persistent LT abnormalities with HAART not detected by measures of peripheral CD4(+) T cell count.     

Implementing a wound care resource nurse program

Nurses are leaders in implementing innovations that can create positive outcomes in the prevention and management of pressure ulcers in patients admitted to acute care hospitals. Believing that nurses knowledgeable in best practices could impact prevalence, incidence, and care of pressure ulcers, an educational program was developed in a Canadian healthcare system to inform and empower nurses providing skin and wound care. The program afforded participants the opportunity to acquire the knowledge and skill to recognize patients at risk for developing pressure ulcers and to independently treat Stage I and Stage II pressure ulcers and skin breakdown related to moisture, friction, and shear. The program includes evidence-based practice recommendations and highlights the Best Practice Guidelines developed by the Registered Nurses Association of Ontario, a provincial body taking an active role in the development, implementation, and evaluation of published guidelines derived from global research literature synthesis. Pre- and post participation assessment of 65 nurse participants from three hospitals deemed the program successful in terms of knowledge and fulfillment of their educational expectations. Organizational support to implement the skin and wound care resource nurse role was encouraging and medical directives for Stage I and Stage II pressure ulcers by nurses were implemented. Evaluation and monitoring of program outcomes, including pressure ulcer incidence rates, continue.     

Randomized clinical trial of abluminus DES+ sirolimus-eluting stent versus everolimus-eluting DES for percutaneous coronary intervention in patients with diabetes mellitus: An optical coherence tomography study

Background

Diabetic patients are at higher risk of recurrent adverse events following percutaneous coronary intervention (PCI) than the nondiabetics. Despite the introduction of new generation drug-eluting stents, their efficacy in the diabetics is still limited.

Aims

To evaluate the efficacy of the Abluminus DES+ biodegradable polymer sirolimus-eluting stent in reducing neointimal hyperplasia in diabetic patients, compared to a durable polymer everolimus-eluting stent (DP-EES).

Methods

A total of 131 patients with diabetes and coronary artery disease were enrolled in six Italian centers and randomized in a 2:1 fashion to PCI with Abluminus DES+ or DP-EES: 85 were assigned to Abluminus DES+ and 46 to DP-EES. The primary endpoint was optimal coherence tomography (OCT)-derived neointimal volume at 9–12 months. Secondary endpoints included OCT-derived neointimal area, neointimal volume obstruction and adverse clinical events.

Results

The primary endpoint, neointimal volume, did not differ between Abluminus DES+ and DP-EES (29.11 ± 18.90 mm³ vs. 25.48 ± 17.04 mm³, p = 0.40) at 9–12-month follow-up. This finding remained consistent after weighing for the sum of stents lengths (1.14 ± 0.68 mm³ vs. 0.99 ± 0.74 mm³ for Abluminus DES+ and DP-EES, respectively, p = 0.38). Similarly, other OCT-derived and clinical secondary endpoints did not significantly differ between the two groups. Rate of target lesion failure was high in both groups (21.2% for Abluminus DES+ and 19.6% for DP-EES).

Conclusions

This preliminary study failed to demonstrate the superiority of the Abluminus DES+ over the DP-EES in diabetic patients in terms of neointimal proliferation.     

Y‐Chromosomal Lineages of Latvians in the Context of the Genetic Variation of the Eastern‐Baltic Region

Variations of the nonrecombining Y‐chromosomal region were investigated in 159 unrelated Baltic‐speaking ethnic Latvians from four different geographic regions, using 28 biallelic markers and 12 short tandem repeats. Eleven different haplogroups (hgs) were detected in a regionally homogeneous Latvian population, among which N1c, R1a, and I1 cover more than 85% of its paternal lineages. When compared its closest geographic neighbors, the composition of the Latvian Y‐chromosomal gene pool was found to be very similar to those of Lithuanians and Estonians. Despite the comparable frequency distribution of hg N1c in Latvians and Lithuanians with the Finno‐Ugric‐speaking populations from the Eastern coast of the Baltic Sea, the observed differences in allelic variances of N1c haplotypes between these two groups are in concordance with the previously stated hypothesis of different dispersal ways of this lineage in the region. More than a third of Latvian paternal lineages belong specifically to a recently defined R1a‐M558 hg, indicating an influence from a common source within Eastern Slavic populations on the formation of the present‐day Latvian Y‐chromosome gene pool.     

Low prevalence of transmitted drug resistance among newly diagnosed HIV-1 patients in Latvia

Transmitted drug resistance (TDR) is a concern because it may reduce the efficacy of antiretroviral treatment. Plasma samples of 119 HIV-1-infected patients who were newly diagnosed at the Infectology Center of Latvia in 2005 and 2006 were analyzed by an in-house genotypic resistance assay to determine the prevalence of TDR in Latvia. TDR was identified using the WHO 2009 list of mutations for surveillance of TDR as implemented in the Stanford Calibrated Population Resistance tool. Neighbor-joining phylogenetic analyses were used to determine genetic subtype and investigate the relatedness of the sequences. Resistance testing was successful in 117 of 119 patients. The study population represented ～20% of all patients that were diagnosed in Latvia in 2005 and 2006 and was well distributed between gender, transmission routes, and areas of residence. Four patients showed evidence of TDR, which represents a prevalence of TDR of 3.4% (95% CI: 0.9-8.5%). All four patients displayed single, but different resistance mutations (M46I, F53L, M41L, and G190A). All patients, except one, were predicted to respond well to standard first-line therapy in Latvia. The prevalence of TDR in Latvia was low, which partly may be due to the low proportion of HIV-1 patients who receive antiretroviral therapy. The results indicate that routine resistance testing in Latvia currently should be focused on patients who display treatment failure, rather than treatment naive patients.     

Performance comparison of two whole genome amplification techniques in frame of multifactor preimplantation genetic testing

Purpose

To compare multiple displacement amplification and OmniPlex whole genome amplification technique performance during array comparative genome hybridization (aCGH), Sanger sequencing, SNaPshot and fragment size analysis downstream applications in frame of multifactor embryo preimplantation genetic testing.

Methods

Preclinical workup included linked short tandem repeat (STR) marker selection and primer design for loci of interest. It was followed by a family haplotyping, after which an in vitro fertilization preimplantation genetic testing (IVF-PGT) cycle was carried out. A total of 62 embryos were retrieved from nine couples with a confirmed single gene disorder being transmitted in their family with various inheritance traits—autosomal dominant (genes—ACTA2, HTT, KRT14), autosomal recessive (genes—ALOX12B, TPP1, GLB1) and X-linked (genes—MTM1, DMD). Whole genome amplification (WGA) for the day 5 embryo trophectoderm single biopsies was carried out by multiple displacement amplification (MDA) or polymerase chain reaction (PCR)-based technology OmniPlex and was used for direct (Sanger sequencing, fragment size analysis, SNaPshot) and indirect mutation assessment (STR marker haplotyping), and embryo aneuploidy testing by array comparative genome hybridization (aCGH).

Results

Family haplotyping revealed informative/semi-informative microsatellite markers for all clinical cases for all types of inheritance. Indirect testing gave a persuasive conclusion for all embryos assessed, which was confirmed through direct testing. The overall allele dropout (ADO) rate was higher for PCR-based WGA, and MDA shows a better genomic recovery scale. Five euploid embryos were subjected to elective single embryo transfer (eSET), which resulted in four clinical pregnancies and birth of two healthy children, which proved free of disease causative variants running in the family postnataly.

Conclusions

A developed multifactor PGT protocol can be adapted and applied to virtually any genetic condition and is capable of improving single gene disorder preimplantation genetic testing in a patient-tailored manner thus increasing pregnancy rates, saving costs and increasing patient reliability.