Citations

ABSTRACT Purpose There is limited evidence regarding the optimal timing of urosymphyseal fistula (USF) repair. Our aim was to conduct a comparative analysis evaluating the postoperative complications and surgical outcomes among patients undergoing surgery for USF, comparing those treated in an early versus delayed fashion. Methods Fifty‐eight patients with diagnosis of USF and who underwent fistula decompression, pubic bone resection, and urinary tract reconstruction were included. Patients who underwent USF repair within 100 days of diagnosis were classified as having early repair, while those treated after 100 days were considered to have delayed repair. Results Thirty‐one underwent delayed USF repair (53.4%), while 27 underwent early repair (46.6%). Most patients were male (96.8%). The median age (72 years vs . 69 years, p = 0.13) and mean BMI (28.7 vs . 28.6, p = 0.97) were comparable between groups. The rate of overall 90‐day complications following USF repair was comparable between groups (77.4% vs . 63%, p = 0.228). We did not find a difference between the rates early complications among groups. The rates of long‐term recurrent pain (46.7% vs . 11.1%, p = 0.004), recurrent osteomyelitis (20% vs . 0%, p = 0.014), and fistula (23.3% vs . 3.7%, p = 0.033) were higher in the delayed USF repair group compared to the early USF repair group. The follow up time was similar between groups too (25.43‐months vs . 32.8‐months, p = 0.257). Conclusion While early USF repair might not affect the incidence of early complications within 90 days post‐surgery, it is associated with reduced rates of long‐term recurrent pain, recurrent osteomyelitis, and fistula recurrence compared to delayed USF repair.

We report that moderate hyperoxia during a critical window of mucociliary differentiation disrupts terminal maturation in neonatal airway epithelial cells cultured in a three-dimensional model. Hyperoxia induces mitochondrial bioenergetic dysfunction and metabolic reprogramming, with proteomic analysis identifying complex I disruption as a key driver of impaired differentiation. Overall, these findings reveal a previously underrecognized link between mitochondrial bioenergetics and airway epithelial development, positioning metabolic dysfunction as an early trigger of hyperoxia-induced neonatal airway injury.

Abstract Background Concerns exist regarding inflatable penile prosthesis (IPP) placement after transcorporal artificial urinary sphincter (TC-AUS) surgery due to potential risk of damaging the AUS cuff during corporal dilation and device placement. Aim To evaluate perioperative complications, infections, revision rates, and device longevity in patients undergoing IPP placement following prior TC-AUS surgery. Methods We present a case series of men who underwent IPP surgery with an existing TC-AUS in place. A retrospective review was conducted of all patients who underwent TC-AUS placement at a single tertiary institution between 2015 and 2025. Patients who subsequently received IPP surgery were identified. Standard IPP techniques were used with additional precautions to protect the AUS, including use of electrocautery instead of sharp dissection and contralateral reservoir placement. Demographics, operative details, complications, infections, revision events, and device survival were collected through review of operative notes and patient records. Outcomes Primary outcomes included intra-operative difficulties, perioperative complications, infection and erosion rates, and revision or failure rates for both the TC-AUS and IPP devices. Results Among 757 TC-AUS placements, 17 patients subsequently underwent IPP surgery. Seven patients (41%) had a history of pelvic irradiation. The median operative time for IPP placement was 83 minutes (interquartile range [IQR] 68-87), and median follow-up was 31.5 months (IQR 11.2-40.6). All reservoirs were positioned contralateral to the AUS reservoir. A 12 Fr catheter was left postoperatively in 10 patients (59%) for <24 hours. Proximal corporal dilation was noted to be challenging in 3 patients (18%) but dilation was completed without cuff injury or corporal perforation. One patient (6%) had TC-AUS cuff erosion 9.5 months after IPP surgery; one patient (6%) experienced TC-AUS device infection 11.5 months after IPP surgery when his AUD pump eroded through the scrotum. Four patients (24%) developed AUS mechanical failure due to cuff leak at a median of 31.9 months after IPP placement (39.9 months post-AUS). Clinical implications IPP implantation following TC-AUS can be performed safely using careful surgical technique, though vigilance for later AUS mechanical failure is warranted. Strengths and limitations This study represents one of the largest single-institution series evaluating IPP after TC-AUS and includes detailed operative and follow-up data. However, its retrospective design, small cohort size, and limited follow-up duration restrict generalizability. Conclusion IPP placement after TC-AUS appears safe, with low infection and erosion rates, though AUS cuff leaks may occur more frequently than when either device is implanted alone.

Abstract Background Subglottic stenosis (SS) is a type of laryngotracheal stenosis defined by a location of less than 1.5 cm below the glottis or the vocal cords. Approximately 20% of cases are idiopathic. Objective We performed a systematic literature review of idiopathic subglottic stenosis (ISS) complicating pregnancy. Search Strategy PubMed, Scopus, and clinicaltrials.gov databases were queried from inception through August 10, 2023 with the following terms: idiopathic subglottic tracheal stenosis, subglottic stenosis, subglottic stenoses, tracheal stenosis, tracheal stenoses, and pregnancy. This systematic review was conducted according to the methods described in the Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) guidelines for reporting systematic reviews. Selection Criteria Studies detailing cases of ISS affecting pregnancy were included and studies reporting SS in pregnancy from a known etiology were excluded. Data Collection and Analysis Our search identified 31 peer‐reviewed published cases of ISS complicating pregnancy that met the inclusion criteria. We also included two additional cases from our institution. Publication bias was checked by the Joanna Briggs Institute critical appraisal tools. Descriptive statistical analyses were performed using Excel. Main Results A majority of patients (26/33, 79%) were diagnosed with ISS during the reported pregnancy. Prior to pregnancy, 20/33 (61%) patients had a working diagnosis or reported symptoms of airway obstruction. Of these patients, 9/20 (45%) carried a diagnosis of asthma, and 6/20 (30%) carried a diagnosis of ISS. Specific symptoms prior to pregnancy were reported in 10/33 (30%) patients. The most common symptoms in these patients were dyspnea (10/10, 100%) and stridor (4/10, 40%). During pregnancy, all patients experienced worsening respiratory symptoms, with dyspnea (31/33, 94%), stridor (18/33, 55%), cough (13/33, 39%), hoarseness (7/33, 21%), and wheeze (5/33, 15%) being the most common symptoms. A total of 22/33 (67%) patients required medical and/or surgical management with dilation and/or excision during pregnancy. Postpartum outcomes were reported in 27/33 (82%) patients, and 1/27 (3.7%) required a tracheostomy immediately postpartum. The majority (18/27, 67%) of these patients required intervention postpartum, while 9/27 (33.3%) were asymptomatic. Conclusion ISS should be considered in pregnant patients with worsening respiratory symptoms despite medical management of asthma. If high clinical suspicion for upper airway obstruction exists, an otolaryngology referral for evaluation with bronchoscopy is recommended.

Abstract Patients with myeloproliferative neoplasms (MPNs) are inherently at increased risk of both thrombotic and bleeding events due to the nature of the condition. Disease management often includes anticoagulants, antiplatelet agents, and/or cytoreductive therapy to mitigate these risks. On the contrary, these therapies can also increase the risk of bleeding, presenting a clinical challenge in balancing the prevention of thrombosis with the management of bleeding complications. The relationship between treatment type, thrombotic events, and bleeding risk remains underexplored in large, real-world populations. This Swedish population-based study aimed to describe how the risk of bleeding in patients living with MPN differs by treatment strategy, and how timing of thrombotic events influences this risk. A total of 15,495 patients diagnosed with MPN between 2006 and 2021, aged 18–90, were identified through the Swedish Cancer Register and the Swedish Patient Register. Bleeding rates were estimated using Cox proportional hazards models with time-split survival data. Treatment categories were defined as follows: no therapy, anticoagulant monotherapy (e.g., warfarin, direct oral anticoagulants [DOACs]); antiplatelet monotherapy (e.g., aspirin, clopidogrel); cytoreductive monotherapy (e.g., hydroxyurea, interferon); and combination therapy, defined as any combination of at least two of the three aforementioned therapies. All treatment categories were compared to anticoagulant monotherapy. Both treatment exposure and thrombotic status were modelled as time-varying covariates, allowing individuals to contribute across multiple thrombosis and treatment combinations over time. Models were adjusted for age at diagnosis, sex, year of diagnosis, and MPN subtype. The cohort was 52% female, with a median age at diagnosis of 71 years (IQR 60–79). The most common MPN subtypes were polycythemia vera (39%) and essential thrombocythemia (38%), followed by MPN-unclassifiable (16%) and primary myelofibrosis (7%). A history of thrombosis at MPN diagnosis was present in 22% of patients, and 19% had a history of bleeding. Among the 10,487 patients receiving combination therapy, the majority included antiplatelet agents: 57% received antiplatelet + cytoreductive therapy, 12% received antiplatelet + anticoagulant therapy, and 22% received all three therapies. Only 8% received anticoagulant + cytoreductive therapy without antiplatelet agents. Patients receiving no therapy had the lowest bleeding rate overall (HR 0.63, 95% CI 0.53–0.75), likely reflecting individuals with less severe disease or contraindications to treatment. Among patients with no thrombotic event, those receiving antiplatelet monotherapy had a 35% lower rate of bleeding compared to those on anticoagulant monotherapy (HR 0.65, 95% CI 0.56–0.76). Combination therapy was associated with a reduced rate of similar magnitude (HR 0.68, 95% CI 0.59–0.78), while cytoreductive monotherapy showed no significant difference (HR 0.96, 95% CI 0.76–1.21). In patients with a prior thrombotic event, antiplatelet monotherapy remained protective (HR 0.59, 95% CI 0.43–0.79), and combination therapy was associated with a slightly lower bleeding rate compared to anticoagulant monotherapy (HR 0.78, 95% CI 0.61–0.99). The estimate for cytoreductive monotherapy in this group (HR 2.04, 95% CI 0.89–4.68) was based on a small number of patients and had wide confidence intervals, limiting interpretability. These findings suggest that bleeding risk in MPN patients is influenced by both treatment type and thrombotic history. Antiplatelet monotherapy and combination therapy were associated with lower bleeding rates than anticoagulant monotherapy, both in patients with and without prior thrombosis, though the effect was more pronounced in those without prior thrombosis. By accounting for the complete patient pathway and modelling treatment and thrombotic status as time-varying exposures, a more accurate representation of real-world treatment dynamics is presented here. Given that the majority of combination therapy regimens included antiplatelet agents, these results underscore the potential protective role of antiplatelet therapy in managing bleeding risk. These insights may support clinical decision-making, and guide personalized treatment strategies and risk assessment in patients diagnosed with MPN.

ABSTRACT Purpose Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath‐held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free‐breathing cardiac MRE. Methods A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k ‐space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post‐processing specialized for cardiac imaging. Results Feasibility of free‐breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant‐specific images, 17‐segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin‐systole), 5.74 ± 0.94, 5.42 ± 0.87 (end‐systole), 3.84 ± 0.71 (begin‐diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end‐diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one‐way, repeated‐measures ANOVA ( p < 0.001) and Friedman's test ( p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject‐specific. Comparison of free‐breathing stiffness measurements against reference breath‐held measurements yielded similar systolic stiffness estimates. Conclusions This study establishes the feasibility of free‐breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject‐specific.

Abstract E1910 evaluated the addition of blinatumomab to chemotherapy in adults with B-acute lymphoblastic leukemia (ALL). The addition of blinatumomab in patients (pts) with measurable residual disease (MRD) negative (neg) B-ALL significantly improved both relapse-free and overall survival (NEJM 2024; 391: 320-33)1. Given the increasing use of blinatumomab and the E1910 backbone chemotherapy regimen, we evaluated &gt; Grade 3 toxicities on this trial in further detail. We assessed toxicity among the MRD-neg pts by age, gender, body mass index (BMI), combined cytogenetic-molecular risk, and number of cycles of blinatumomab received. We also evaluated toxicities during induction since this trial used a modified chemotherapy backbone. Methods: The eligibility, combined cytogenetic-molecular risk, and treatment have been previously described.1 All toxicities were &gt; Grade 3 by CTCAE version 4 with at least a possible relationship to treatment. Descriptive statistics were used to summarize the occurrence and rates of toxicities and Fisher's exact test was used to compare differences in proportions between groups. Analysis of induction included all pts who started treatment. Analysis of Step 3 toxicities included MRD-neg pts who started treatment on the blinatumomab (n=111) or chemotherapy only arm (n=112). Results: Pt characteristics: For induction (n=488), median age was 51 years (yrs) (range 30-70); 48.6% female. Combined cytogenetic-molecular risk: favorable (13.5%); intermediate (12.9%); no risk assigned (16.2%); unfavorable (57.4%). For induction, we compared toxicities for E1910 (n=488) to pts treated on a prior young adult study (n=289) (C10403) (Blood Adv 2021; 5(2): 504-12). The incidence of hyperglycemia (8% vs. 31.1%, p&lt; 0.001), aspartate aminotransferase (AST) increase (6.1% vs. 12.8%, p=0.002), alanine aminotransferase increase (ALT) (11.7% vs. 28.7%, p&lt; 0.001), and hyperbilirubinemia (11% vs. 19%, p=0.002) were significantly lower in E1910 pts. The incidence of pancreatitis (1.8%), thromboembolic events (4.5%), and febrile neutropenia (25.4%) in E1910 was similar to C10403. Toxicities in the MRD-neg pts in the blinatumomab arm (n=111): Despite a high incidence of neutropenia (74.8%) and thrombocytopenia (55.9%) in Step 3, there was a relatively low incidence of sepsis (7.2%), bacteremia (1.8%), cytokine release syndrome (CRS) (3.6%) and neurologic adverse events (0-6.3%). There was a higher incidence of neurological or psychiatric events in the blinatumomab arm (23%) versus chemotherapy arm (5%) (p &lt; 0.001) when all events were combined. There was a numerically higher incidence of ataxia (4.4% vs. %, p=0.16) and dysphasia (11.1% vs. 3%, p=0.12) in pts &gt; 55 yrs and a higher incidence of neutropenia (80.3% vs. 66.7%, p=0.12) and thrombocytopenia (62.1% vs. 46.7%, p=0.12) in the younger pts (age &lt; 55 yrs). In pts with a BMI &lt; 30 kg/m2 (vs. &gt; 30 kg/m2), there was a significantly higher incidence of leukopenia (51.7% vs. 26.4%, p=0.007) and thrombocytopenia (65.5% vs. 45.3%, p=0.037). However, this did not translate into an increased incidence of bleeding or infectious complications. By gender, females had a higher numerical incidence of AST increase (8.8% vs. 0%, p=0.057) and CRS (7% vs. 0% p=0.12); whereas males had a higher incidence of catheter- related infections (7.4% vs. 0%, p=0.05) and hyperglycemia (11.1% vs. 3.5%, p=0.16). A little more than half (56.8%) of pts received 4 cycles of blinatumomab with the remainder of pts receiving 1 (10.8%), 2 (28.8%), or 3 cycles (3.6%). Pts receiving 3-4 cycles of blinatumomab vs. 1-2 cycles of blinatumomab had a statistically higher incidence of anemia (38.8% vs. 6.8%, p&lt; 0.001), neutropenia (98.5% vs. 38.6%, p&lt; 0.001), and thrombocytopenia (83.6% vs. 13.6%, p&lt; 0.001), likely related to being on treatment for a longer period of time. Conclusions: Blinatumomab was well tolerated with no significant toxicity differences noted by age, gender, or number of cycles of blinatumomab received. Pts with a lower BMI did have an increased incidence of leukopenia and thrombocytopenia, possibly related to flat dosing of the drug. However, this did not translate into increased complications. Toxicites during induction were notably few, which suggests that this backbone with age adjustments may serve as a good backbone for future trials. Blinatumomab is being evaluated with low dose chemotherapy and other targeted agents in ongoing trials.

Abstract BACKGROUND Early disease progression within 24 months following chemoimmunotherapy (CIT) is an established adverse prognostic factor for overall survival (OS) in patients (pts) with indolent non-Hodgkin lymphomas. Initially reported in pts with follicular lymphoma, progression of disease (PD) within 24 months in pts with CLL treated with CIT (occurring in ~1-out-of-4 pts) is also associated with inferior OS. The prognostic utility of early event status in pts with CLL treated with targeted therapies is unknown. Recently, we reported worse than expected outcomes with BCL2 inhibitor (BCL2i) treatments in an international cohort of pts with covalent BTK inhibitor (BTKi)-resistant, CIT-naïve CLL. We hypothesize that early disease progression on first-line (1L) targeted agent treatment will identify additional pts with high-risk disease beyond conventional prognostics in the current era. METHODS We identified pts in the Mayo Clinic CLL Database with the following 1L treatments a) BTKi (+/- anti-CD20 monoclonal antibody [CD20mAb]); b) BCL2i + CD20mAb; c) BTKi + BCL2i +/- CD20mAb. PD was defined by a) new or progressive lymphadenopathy or splenomegaly; and/or b) ≥ 50% increase from nadir absolute lymphocyte count (ALC) with persistent (&gt;2 months), and otherwise unexplained ALC ≥ 10x109/L; and/or c) Richter transformation. Logistic regression model evaluated association between clinical factors and POD36 status. OS in pts with PD within 36 months of 1L start (POD36) was evaluated and compared to those without early PD (non-POD36) with analyses: a) starting from time of PD (POD36) and starting from 3 years after 1L initiation (non-POD36); and b) Kaplan-Meier landmark analysis amongst pts alive 3 years post 1L initiation. Cox regression analyses compared a) OS from POD36 by groups and b) OS from 1L treatment with POD36 as a time-dependent covariate. RESULTS A total of 787 pts with CLL initiated 1L targeted therapy (n=538 [68%] BTKi +/- CD20mAb; n=151 [19%] BCL2i + CD20mAb; n=98 [13%] BTKi + BCL2i +/- CD20mAb. The median age at 1L start was 67 years (range 26-92 years), and 67% of pts were male. Among pts with complete CLL-IPI data (n=519), 44% and 15% had high- and very high-risk CLL-IPI risk scores, respectively. Specific pre-1L treatment disease characteristics included TP53 disruption (del17p or TP53 mutation) in 120/639 (19%), del11q in 103/634 (16%), unmutated IGHV in 406/591 (69%), complex karyotype (≥3 clonal structural or numerical abnormalities on karyotype) in 70/273 (26%), and positive CD49d expression in 229/449 (46%). The median pre-treatment beta-2-microglobulin level was 3.3 mcg/mL (range 1.2-24.4 mcg/mL). The median follow-up from 1L start was 50 months (95% CI 46-54 months). 496 pts met criteria for defining POD36 status; 72 (15%) had PD, and 424 did not. TP53 disruption (OR 2.9; 95% CI 1.5-5.7, P=0.001) was associated with POD36 on univariate analysis; complex karyotype, unmutated IGHV status, elevated serum lactate dehydrogenase level, age, sex, and inclusion of CD20mAb were not associated with POD36 status. Median OS from the time of determination of POD36 status was not reached. OS was significantly shorter after POD36 compared to non-POD36 pts (HR 3.5; 95%CI 2.1-6.0, P&lt;0.0001), with 4-year OS estimates of 65% and 88%, respectively. When assessed by landmark analysis at the 3-year timepoint following 1L start (n=50 POD36), OS was also shorter in pts with POD36 compared to non-POD36 pts (HR 3.5; 95%CI 1.8-6.8, P=0.0002). In the overall cohort (n=787), when evaluating OS from 1L treatment with POD36 as a time-dependent covariate, POD36 status was associated with an increased risk of death (HR 4.3; 95% CI 2.6-7.1, P&lt;0.0001) on univariable analysis; and remained an independent marker of shorter OS in multivariable analyses after adjusting for age, sex, TP53 disruption status, and IGHV status (HR 4.2; 95% CI 2.1-8.4, P&lt;0.0001). CONCLUSIONMost pts achieved durable CLL disease control with 1L targeted treatments, and early PD occurs much less frequently than previously reported with CIT. However, among pts who receive 1L targeted therapies for CLL, PD within 36 months is associated with a ~4-fold higher risk of death. These results, if validated in larger data sets, will provide a practical measure for identifying a high-risk subgroup of pts in need of novel treatment strategies in future trials.