Citations

Abstract Erdheim-Chester disease (ECD) is a rare systemic histiocytic neoplasm, with cardiac morbidities, including cardiovascular (CV) risk factors and cardiac conditions, playing a significant yet poorly understood role in the disease burden. This study evaluated the prevalence, characteristics, and prognosis of ECD in patients with (ECD-C) and without cardiac involvement (ECD-noC) and compared the burden of cardiac morbidities with matched controls. Patients diagnosed with ECD between 1990 and 2021 at a tertiary center were included, with cardiac involvement centrally assessed using radiographic studies. Cardiac morbidities were compared with a control group without ECD, matched for age, sex, body mass index, and smoking history. Among 104 patients with ECD, 39 (37%) had cardiac involvement. Patients with ECD-C had higher rates of hypertension (67% vs 46%), hyperlipidemia (67% vs 40%), heart failure (36% vs 8%), and pericardial effusion (28% vs 2%) than those with ECD-noC. Compared with the matched non-ECD cohort, patients with ECD had higher prevalence of coronary artery disease (20% vs 7%), heart failure (18% vs 4%), and antihypertensive drug use (55% vs 40%). Notably, patients with ECD-C had inferior progression-free survival (PFS) from frontline therapy compared with patients with ECD-noC (5-year PFS, 28.3% vs 70.5%). These findings highlight the burden of CV risk factors and cardiac conditions in ECD, even without a clinical diagnosis of ECD-C. Importantly, this cardiac morbidity burden is substantial for patients with ECD-C compared with ECD-noC. Our findings highlight the need for comprehensive cardiac risk assessment and management strategies to improve patient outcomes.

ABSTRACT Hepatopulmonary syndrome (HPS) affects up to one‐third of patients with advanced chronic liver disease (ACLD) and is an independent risk factor for increased mortality. While HPS often improves following liver transplantation, patients with severe or very severe HPS—classified by partial pressure of arterial oxygen (PaO 2 ) <60 mmHg—face higher post‐transplant complications and mortality. However, evidence suggests that even patients with severe HPS may benefit from liver transplantation when performed at high‐volume centers. To assess post‐transplant outcomes in this population, we conducted a retrospective chart review of 20 patients diagnosed with severe or very severe HPS who underwent liver transplantation at Mayo Clinic Hospital in Arizona between 2014 and 2024. The most common post‐transplant complication was persistent hypoxemia, managed on a case‐by‐case basis with various treatments, though no single approach proved consistently superior. All patients who received transplants demonstrated improvement; 84% of patients ultimately discontinued supplemental oxygen, with a mean time of 250 days (range: 0–1113 days). Time was the key factor in recovery. Notably, no deaths in our cohort were directly attributed to HPS. These findings support liver transplantation as a viable treatment option for HPS, even in severe cases, and underscore the importance of experienced transplant centers in optimizing patient outcomes.

This case describes a 74-year-old woman who developed post-surgical acute respiratory distress syndrome (ARDS) after Photodynamic Bone Stabilization System (PBSS) a balloon rupture with extravasation of approximately 20 mL of monomeric resin. The ARDS likely resulted from 2 possibilities: (1) displacement of fat or tumor embolism from PBSS insertion/inflation, displacement from bioinert monomers, or orthopedic screws; or (2) chemical inflammation/pneumonitis due to intravascular dissemination of bioinert monomeric resin. Though balloon rupture and/or fat embolism is a stated manufacturer risk, (IlluminOss. Accessed May 19, 2025. https://illuminoss.com/uploads/nuggets/60e47f517ee33862a5fcaab8/900356_T.pdf) this is the first published human case report of ARDS as a complication of PBSS balloon rupture.

We describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistant (MDR) Staphylococcus epidermidis hip PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDR S. epidermidis. We developed a novel phage therapy protocol for this patient, with twice daily, intra-articular and intravenous (7 × 109 PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Twelve months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection.

Background Patients with advanced cancer experience a substantial amount of existential and emotional distress. Dignity therapy (DT) is a brief, individualized psychotherapy that aims to relieve existential distress and improve the experiences of individuals impacted by serious illness. Aim To evaluate the feasibility and acceptability of virtual DT (vDT) among patients with advanced cancer. Methods This pilot study recruited adult patients with advanced cancer and an expected prognosis >6 months. The vDT intervention consisted of 2 sessions of guided interviews focused on life review, discussion, and development of a generativity document (GD). Feasibility and acceptability were assessed quantitatively and with semi-structured interviews. Effectiveness measures (distress, dignity impact scale, quality of life [QOL]) were administered pre/post intervention. Results Thirty-one patients referred from a palliative care clinic were eligible. Twenty-one consented and 15 received a final GD. Patients who completed final assessments (N = 9) reported satisfaction with their experience and would recommend the therapy to others. Patients found the virtual component of the intervention acceptable, and the majority noted an improvement in their dignity. Qualitative analysis revealed themes of study team effectiveness, perspectives on intervention processes, benefits to self, and benefits to loved ones. Conclusion Participation in vDT intervention was feasible and acceptable for patients. Patients appreciated the connection with the interviewer, the process, and the benefit of having a document to share with loved ones. Preliminary effectiveness data suggest vDT improves sense of dignity.

Abstract Rationale Pulmonary hypertension (PH) in interstitial lung disease (ILD) lacks approved therapies. Objectives The Pulmonary Vascular Research Institute GoDeep metaregistry collects real-world data of patients with PH from international PH referral centers. Methods Patients with ILD-PH and relevant subgroups (idiopathic interstitial pneumonia [IIP], idiopathic pulmonary fibrosis [IPF]) were stratified by pulmonary vascular resistance (PVR). Kaplan-Meier survival analyses and adjusted Cox proportional hazards models were employed, additionally accounting for immortal time bias, sensitivity analyses, Heller explained relative risk statistics, and target trial emulation framework analysis. Measurements and Main Results Among 34,482 patients, 940 with hemodynamically fully characterized incident ILD-PH (median age, 67 [IQR, 59–74] yr) were identified. A total of 62% had severe ILD-PH with PVR &gt;5 Wood units (WU) and poor survival rates (29% and 18% at 3 and 5 yr), significantly worse than patients with ILD-PH with PVR ≤5 WU and patients with pulmonary arterial hypertension. Survival was poorest in severe IPF-PH. A total of 59% of all patients ILD-PH received PH-targeted therapy, predominantly phosphodiesterase-5 inhibitors (PDE5is). PDE5i treatment was consistently associated with significantly improved survival in patients with severe PH (hazard ratios of 0.537 [0.370–0.781], 0.461 [0.233–0.913], and 0.435 [0.215–0.8] for IIP-PH, IPF-PH, and IIP-PH with nintedanib/pirfenidone background therapy), but not in patients with less severe hemodynamic impairment, supported by sensitivity analyses, Heller statistics, and target trial emulation framework analysis. The survival statistics of patients with PDE5i-treated IIP-PH or IPF-PH were validated in the independent COMPERA registry. Combination therapy with PDE5is and inhaled prostacyclin analogues was superior to monotherapy using PDE5is (hazard ratio, 0.341; 0.205–0.566). Conclusions Prognosis in ILD-PH was generally very poor and was related to PH severity. PDE5i treatment in severe IIP-PH and IPF-PH was associated with improved survival, which is to be further verified in controlled trials.

Objectives: To investigate the association between hormone therapy use and severe outcomes due to COVID-19 in perimenopausal and postmenopausal women. Methods: Using the Rochester Epidemiology Project, we retrospectively searched for the records of women aged 40-65 years who had a documented case of COVID-19 between March 12 and September 29, 2020. We further identified those who were perimenopausal or postmenopausal. The rates of emergency department visits, hospitalizations, and deaths were compared by hormone therapy use. Logistic regression models were used to assess the odds of the combined outcome based on hormone therapy use. Results: Among the 689 patients included in this study, the median age was 56 years, and 77.5% were White. Compared with patients currently using hormone therapy, those with past/never use of hormone therapy were significantly older, had more risk factors for severe COVID-19, and had a higher incidence of diabetes. A total of 102 emergency department visits/hospitalizations/deaths occurred among both groups. Participants with current hormone therapy use had similar rates and risk of emergency department/hospitalization/death outcomes as those without hormone therapy, even after adjusting for age and severe COVID-19 risk factors. Conclusions: Severe COVID-19 outcomes were not significantly different between women with current versus past/never use of hormone therapy. Our study adds to the data suggesting no harm with hormone therapy use in women with severe symptoms of COVID-19.

Intronic GGGGCC hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Despite its intronic location, this repeat avidly supports synthesis of pathogenic dipeptide repeat (DPR) proteins via repeat-associated non-AUG (RAN) translation. However, the template RNA species that undergoes RAN translation endogenously remains unclear. Using long-read based 5′ RNA ligase-mediated rapid amplification of cDNA ends (5′ Repeat-RLM-RACE), we identified C9orf72 transcripts initiating within intron 1 in a C9BAC mouse model, patient-derived iNeurons, and iNeuron-derived polysomes. These cryptic m 7 G-capped mRNAs are at least partially polyadenylated and are more abundant than transcripts derived from intron retention or circular intron lariats. In RAN translation reporter assays, intronic template transcripts–even those with short (32 nucleotide) leaders–exhibited robust expression compared to exon–intron and repeat-containing lariat reporters. To assess endogenous repeat-containing lariat RNA contributions to RAN translation, we enhanced endogenous lariat stability by knocking down the lariat debranching enzyme Dbr1. However, this modulation did not impact DPR production in patient-derived iNeurons. These findings identify cryptic, linear, m 7 G-capped intron-initiating C9orf72 mRNAs as an endogenous template for RAN translation and DPR production, with implications for disease pathogenesis and therapeutic development.