RESULTS: Women and girls comprise one-third of people who use and inject drugs globally. There is substantial variation in HIV prevalence in this population, between and within countries. There is a pronounced lack of data examining HIV risk among particularly vulnerable subpopulations of women who use and inject drugs, including women who have sex with women, transgender women, racial and ethnic minority women, and young women. Women who use and inject drugs experience stigma and discrimination that affect access to services, and high levels of sexual risk exposures.
CONCLUSIONS: There are significant gaps in our understanding of the epidemiology of drug use and injecting among women and girls and HIV risk and prevalence in this population. Women are frequently underrepresented in studies of drug use and HIV risk and prevalence among people who inject drugs, limiting our understanding of possible sex differences in this population. Most research originates from developed countries and may not be generalizable to other settings. A great deal of work is needed to improve understanding of HIV among particularly vulnerable subpopulations, such as transgender women who use drugs. Better data are critical to efforts to advocate for the needs of women and girls who use and inject drugs.
OBJECTIVE: The purpose of this study was to evaluate the initial learning experience and acute procedural success in adopting this procedure in an academic training center.
METHODS: A retrospective review of LBBAP procedures using the Biotronik Solia stylet-driven lead from June 2022 to December 2023 was performed. Procedural and fluoroscopy times with electrocardiographic and pacing parameters were evaluated to determine safety and acute procedural outcomes.
RESULTS: A total of 69 patients (mean age 75 ± 12 years; 60.9% male) underwent LBBAP implantation over 18 months for standard pacing indications by 10 implanters (including 7 fellows-in-training) without previous experience in LBBAP technique. Mean total procedural time was 74.1 ± 23.5 minutes, and mean fluoroscopy time for LBBAP lead insertion was 9.3 ± 5.4 minutes. Mean paced QRS duration was 115.2 ± 15.5 ms, and mean left ventricular activation time was 79.4 ± 14.5 ms. An rsR' pattern was achieved in 76.8%. LBBAP was successful in 78.3% (overall 43.5% single deployment; median 2 [interquartile range 1-3]) with excellent LBBAP lead parameters: threshold 0.8 ± 0.4 V at 0.4 ms; sensing 9.4 ± 4.2 mV; impedance 627 ± 131 Ω. Acute procedural complications included damaged lead helix requiring a second lead (4.3%), pneumothorax (2.9%), and acute LBBAP lead dislodgment (1.4%). Septal perforation occurred in 10.1% of cases with no acute sequelae. When analyzed in tertiles, the number of lead deployment attempts was significantly reduced with no changes to procedural success rates with increasing experience.
CONCLUSION: Adoption of LBBAP with stylet-driven lead in an academic training center is feasible and safe, with satisfactory success rates and no overly steep learning curve.
OBJECTIVE: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.
METHODS: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.
RESULTS: Prenatal features included hypokinesia or akinesia and growth restriction. Six pregnancies were terminated. Nine infants were born at or near term with severe-to-profound weakness and required resuscitation. Seven died following withdrawal of life support. Two surviving children require ongoing respiratory support. Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression. The exceptions, from 2 unrelated families, had homozygous truncating variants predicted to induce complete nonsense mediated decay. However, subsequent analyses suggested that the causative variant in each family had an additional previously unrecognized impact on splicing likely to result in some near-normal-length titin expression. This impact was confirmed by minigene assay for 1 variant.
INTERPRETATION: This study confirms the clinical variability of congenital titinopathy. Severely affected individuals succumb prenatally/during infancy, whereas others survive into adulthood. It is likely that this variability is because of differences in the amount and/or length of expressed titin. If confirmed, analysis of titin expression could facilitate clinical prediction and increasing expression might be an effective treatment strategy. Our findings also further-support the hypothesis that some near-normal-length titin expression is essential to early prenatal survival. Sometimes expression of normal/near-normal-length titin is due to disease-causing variants having an additional impact on splicing. ANN NEUROL 2025;97:611-628.