Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy.

Background: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States; little is known about pregnancy outcomes with modulator use. The aim of this retrospective study was to determine the impact of CFTR modulators on maternal outcomes.

Research Question: Does pregnancy differentially affect outcomes in female subjects with CF with and without CFTR modulator exposure?

Study Design And Methods: Data on pregnancies from 2010 to 2021 were collected from 11 US adult CF centers.

A Qualitative Exploration of Women With Cystic Fibrosis and Urinary Incontinence.

Importance: Women with cystic fibrosis (CF) historically experience a high prevalence of urinary incontinence (UI). However, this area is understudied, especially in the modern era of highly effective modulator therapy (HEMT).

Objective: This study aimed to explore the UI experiences, knowledge, care-seeking behavior, and treatment preferences of women with CF.

Outcomes of single vs double lung retransplantation in patients with cystic fibrosis.

Background: Patients requiring lung transplant for cystic fibrosis (CF) may require retransplant due to limited graft survival and otherwise excellent life expectancy. Optimal transplant strategy for this population, including single vs double lung retransplant, has not been established.

Methods: We performed a retrospective analysis of the United Network for Organ Sharing/Organ Procurement and Transplant Network (UNOS/OPTN) database to identify adult lung retransplant recipients from 2005 to 2021 with a primary diagnosis of CF.

Technical Development and In Silico Implementation of SyntheticMR in Head and Neck Adaptive Radiation Therapy: A Prospective R-IDEAL Stage 0/1 Technology Development Report.

Objective: The purpose of this study was to investigate the technical feasibility of integrating the quantitative maps available from SyntheticMR into the head and neck adaptive radiation oncology workflow. While SyntheticMR has been investigated for diagnostic applications, no studies have investigated its feasibility and potential for MR-Simulation or MR-Linac workflow. Demonstrating the feasibility of using this technique will facilitate rapid quantitative biomarker extraction which can be leveraged to guide adaptive radiation therapy decision making.

Prioritizing sexual and reproductive health research and care for people with cystic fibrosis: A 2023 workshop report from the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender (SHARING) Research Working Group.

Background: To address sexual and reproductive health (SRH) concerns among people with cystic fibrosis(PwCF), the CF Foundation created the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group. This report summarizes CF community SRH research priorities and workshop discussions/future study planning.

Methods: Pre-workshop, we distributed a community prioritization survey on CF SRH research/care.

Adjunctive Systemic Corticosteroids for Pulmonary Exacerbations of Cystic Fibrosis.

Pulmonary exacerbations (PEx) remain the most common cause of morbidity, recurrent hospitalization, and diminished survival in people with cystic fibrosis (PWCF) and are characterized by excess inflammation. Corticosteroids are potent, widely available antiinflammatory drugs. However, corticosteroid efficacy data from randomized controlled trials in PWCF are limited.

Prevalence and Clinical Impact of Respiratory Viral Infections from the STOP2 Study of Cystic Fibrosis Pulmonary Exacerbations.

Rates of viral respiratory infection (VRI) are similar in people with cystic fibrosis (CF) and the general population; however, the associations between VRI and CF pulmonary exacerbations (PEx) require further elucidation. To determine VRI prevalence during CF PEx and evaluate associations between VRI, clinical presentation, and treatment response. The STOP2 (Standardized Treatment of Pulmonary Exacerbations II) study was a multicenter randomized trial to evaluate different durations of intravenous antibiotic therapy for PEx.

Clinician perspectives and practices related to sexual and reproductive care provision for males with cystic fibrosis.

Background: Males with cystic fibrosis (MwCF) have unique sexual and reproductive health (SRH) concerns. This study investigates multidisciplinary CF clinician perspectives related to SRH for MwCF in the current era of CF care.

Methods: We surveyed multidisciplinary clinicians exploring attitudes, practices, and preferences toward male CF SRH care.

A provider survey assessing fetal impact of CFTR modulator use in males with CF during assisted and unassisted reproduction and partner pregnancy.

Background: Most males with cystic fibrosis (mwCF) are infertile but with CF transmembrane conductance regulator (CFTR) modulator-conferred benefits, more are utilizing assisted reproductive technologies (ART). Administration of normal human doses of modulators in animal reproductive models caused no genotoxicity; no human data exists. Potential health decline following modulator discontinuation makes the decision to withhold therapy during reproduction challenging.

Respiratory compromise in French bulldogs presented with intervertebral disc extrusion.

Background: French bulldogs hospitalised for the management of intervertebral disc extrusion (IVDE) are frequently affected by respiratory compromise, typically brachycephalic-associated upper respiratory obstruction and/or aspiration events. We evaluated the occurrence of such respiratory compromise events in French bulldogs presented to two referral hospitals.

Methods: Clinical data for French bulldogs diagnosed with IVDE were retrospectively collated, including severity of neurological deficits, neuroanatomical localisation, diagnosis, details of respiratory compromise, treatment and outcome.

Interval Sentinel Lymph Nodes With the Use of Routine Lymphoscintigraphy in Extremity Melanoma.

Introduction: Lymphoscintigraphy (LS) helps identify drainage to interval (epitrochlear or popliteal) lymph node basins for extremity melanomas. This study evaluated how often routine LS evaluation identified an interval sentinel lymph node (SLN) and how often that node was found to have metastasis.

Methods: A single institution, retrospective study identified patients with an extremity melanoma who underwent routine LS and SLN biopsy over a 25-y period.

Characteristics associated with cystic fibrosis-related pulmonary exacerbation treatment location.

Previous studies indicate that hospital rather than home treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) can improve outcomes. We evaluated characteristics of adult participants from the Standardized Treatment of Pulmonary Exacerbations (STOP2) trial with two separate comparisons: (1) those who were treated initially in hospital (N = 768) to those treated initially at home (N = 214) and (2) those treated only in hospital (N = 328) to those who were treated only at home or both at home and in hospital (N = 654). Participants who had Medicaid insurance, were treated for shorter duration, and traveled longer to reach treatment centers were more likely to have been treated initially in the hospital.

Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.

Background/aims: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung.

Plain language summary of the INCREASE study: inhaled treprostinil (Tyvaso) for the treatment of pulmonary hypertension due to interstitial lung disease.

What Is This Summary About?: Here, we summarize the results from the INCREASE study, originally published in the . The INCREASE study looked at how well a medication called inhaled treprostinil works and how safe it is, compared to placebo (a fake medication), in adults who have pulmonary hypertension associated with interstitial lung disease or PH-ILD.

What Were The Results?: A total of 326 participants took part in the study.

Impact of lumacaftor/ivacaftor and tezacaftor/ivacaftor on treatment response in pulmonary exacerbations of F508del/F508del cystic fibrosis.

Background: Pulmonary exacerbations (PEx) remain a major cause of morbidity and mortality in people with cystic fibrosis (PWCF). Although the combination cystic fibrosis transmembrane conductance regulator (CFTR) modulators lumacaftor/ivacaftor and tezacaftor/ivacaftor have been shown to reduce PEx frequency, their influence on clinical and biochemical responses to acute PEx treatment is unknown.

Methods: We performed a secondary analysis of STOP2, a large multicenter randomized controlled trial of antimicrobial treatment durations for adult PWCF presenting with PEx.

Extracellular vesicles enhance pulmonary transduction of stably associated adeno-associated virus following intratracheal administration.

Adeno-associated virus (AAV) vector has shown multiple clinical breakthroughs, but its clinical implementation in inhaled gene therapy remains elusive due to difficulty in transducing lung airway cells. We demonstrate here AAV serotype 6 (AAV6) associated with extracellular vesicles (EVs) and secreted from vector-producing HEK-293 cells during vector preparation (EVAAV6) as a safe and highly efficacious gene delivery platform for inhaled gene therapy applications. Specifically, we discovered that EVAAV6 provided markedly enhanced reporter transgene expression in mucus-covered air-liquid interface (ALI) cultures of primary human bronchial and nasal epithelial cells as well as in mouse lung airways compared to standard preparations of AAV6 alone.

Non-traumatic hemorrhagic myelopathy in dogs.

Background: Non-traumatic spinal cord hemorrhage (NTSH) is an uncommon cause of myelopathy in dogs.

Objectives: Describe the clinical characteristics, concurrent medical conditions and underlying causes, magnetic resonance imaging (MRI) findings and outcome in dogs with NTSH.

Animals: Dogs diagnosed with NTSH using gradient echo T2-weighted (GRE) sequences with or without histopathological confirmation of hemorrhage were included.

Association between unplanned pregnancies and maternal exacerbations in cystic fibrosis.

Introduction: Following availability of the highly effective cystic fibrosis (CF) transmembrane conductance regulator modulator, elexacaftor/tezacaftor/ivacaftor, there was a near doubling of pregnancies reported in the United States (US) in people with CF. We sought to determine health impacts of planned (PP) versus unplanned pregnancies (UP).

Methods: We collected retrospective pregnancy data from January 2010-December 2020 from 11 US CF centers.

Complications and Practice Variation in the Use of Peripherally Inserted Central Venous Catheters in People With Cystic Fibrosis: The Prospective Study of Peripherally Inserted Venous Catheters in People With Cystic Fibrosis Study.

Background: Peripherally inserted central catheters (PICCs) are used commonly to administer antibiotics to people with cystic fibrosis (CF), but their use can be complicated by venous thrombosis and catheter occlusion.

Research Question: Which participant-, catheter-, and catheter management-level attributes are associated with increased risk of complications of PICCs among people with CF?

Study Design And Methods: This was a prospective observational study of adults and children with CF who received PICCs at 10 CF care centers in the United States. The primary end point was defined as occlusion of the catheter resulting in unplanned removal, symptomatic venous thrombosis in the extremity containing the catheter, or both.

Breast Implants Save Lives: Gunshot Wound to a Silicone Gel Implant.

What is the incidence of gunshot injuries involving breast implants?What are the considerations for managing a patient with a gunshot wound to a breast implant?Can a breast implant alter the trajectory of a bullet to the chest?What are the considerations for reconstructing a breast after a gunshot wound?

Prevalence and Risk Factors for Low Bone Mineral Density in Adults With Cystic Fibrosis.

Single-center studies have suggested that up to 70% of adults with cystic fibrosis (CF) have lower than expected bone mineral density (BMD), substantially higher than the 25% prevalence reported from national registries. We determined the prevalence of low BMD in CF adults at our center and assessed risk factors for low BMD. This retrospective cohort study was conducted in all CF patients ≥18 years of age who had a dual-energy X-ray absorptiometry (DXA) scan performed at the Johns Hopkins Adult Cystic Fibrosis center between 2010 and 2018.

Downstream Alternate Start Site Allows N-Terminal Nonsense Variants to Escape NMD and Results in Functional Recovery by Readthrough and Modulator Combination.

Genetic variants that introduce premature termination codons (PTCs) have remained difficult to therapeutically target due to lack of protein product. Nonsense mediated mRNA decay (NMD) targets PTC-bearing transcripts to reduce the potentially damaging effects of truncated proteins. Readthrough compounds have been tested on PTC-generating variants in attempt to permit translation through a premature stop.

Variation in reproductive mode across the latitudinal range of invasive Russian knapweed.

For invading species, reproduction is a critical determinant of population establishment as well as spread into new areas. When species have multiple modes of reproduction, the prevalence of different modes can influence management decisions. We used genetic markers to determine the prevalent method of recruitment for invasive Russian knapweed ().