Citations

AbstractBackgroundHemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloantibody‐mediated destruction of fetal/neonatal red blood cells (RBCs). While the pathophysiology has been well‐characterized, the clinical and laboratory monitoring practices are inconsistent.MethodsWe surveyed 103 US institutions to characterize laboratory testing practices for individuals with fetuses at risk of HDFN. Questions included antibody testing and titration methodologies, the use of critical titers, paternal and cell‐free fetal DNA testing, and result reporting and documentation practices.ResultsThe response rate was 44% (45/103). Most respondents (96%, 43/45) assess maternal antibody titers, primarily using conventional tube‐based methods only (79%, 34/43). Among respondents, 51% (23/45) rescreen all individuals for antibodies in the third trimester, and 60% (27/45) perform paternal RBC antigen testing. A minority (27%, 12/45) utilize cell‐free fetal DNA (cffDNA) testing to predict fetal antigen status. Maternal antibody titers are performed even when the fetus is not considered to be at risk of HDFN based on cffDNA or paternal RBC antigen testing at 23% (10/43) of sites that assess titers.DiscussionThere is heterogeneity across US institutions regarding the testing, monitoring, and reporting practices for pregnant individuals with fetuses at risk of HDFN, including the use of antibody titers in screening and monitoring programs, the use of paternal RBC antigen testing and cffDNA, and documentation of fetal antigen results. Standardization of laboratory testing protocols and closer collaboration between the blood bank and transfusion medicine service and the obstetric/maternal‐fetal medicine service are needed.

Background Debridement, antibiotics, and implant retention (DAIR) is used to manage acute periprosthetic joint infections (PJIs) after total joint arthroplasty (TJA). Given the uncertain success of single or multiple DAIR attempts and possible long-term deleterious effects this treatment can create when trying to treat persistent infection, it is important to understand the frequency with which surgeons in the United States are attempting multiple debridements for PJI and whether those procedures are achieving the desired goal. Question/purposes In the context of the American Joint Replacement Registry (AJRR), we asked: (1) What proportion of patients who undergo DAIR have only one DAIR, and what percentage of those patients have more than one? (2) Of the patients who undergo one or more DAIR procedures, what is the proportion who progress to additional surgical procedures? (3) What is the cumulative incidence of medical or surgical endpoints related to infection on the affected leg (other than additional DAIR procedures)? Methods DAIR procedures to treat PJI, defined by ICD-9/10 and CPT (Current Procedural Technology) codes, reported to the AJRR from 2012 to 2020 were merged with Centers for Medicare and Medicaid Services (CMS) data from 2012 to 2020 to determine the incidence of patients aged 65 and older who underwent additional PJI-related procedures on the same joint. Linking to CMS ensures no loss to follow-up or patient migration to a non-AJRR site. As of 2021, the AJRR captures roughly 35% of all arthroplasty procedures performed in the United States. Of the total 2.2 million procedures in the AJRR, only 0.2% of the procedures were eligible based on our inclusion criteria. Additionally, 61% of the total population is Medicare eligible, and thus, these patients are linked to CMS. Of the 5029 DAIR attempts after a TKA, 46% (2318) were performed in female patients. Similarly, there were a total of 798 DAIR attempts after a THA, and 50% (398) were performed in female patients. For the purposes of decreasing confounding factors, bilateral THAs and TKAs were excluded from the study population. When querying for eligible procedures from 2012 to 2020, the patient population was limited to those 65 years and older, and a subsequent reoperation for infection had to be reported after a primary TJA. This limited the patient population as most infections reported to AJRR resulted in a revision, and we were searching for DAIRs. Although 5827 TJAs were identified as a primary TJA with a subsequent infectious event, more than 65% (3788) of that population did not have a reported event. The following conditions were queried as secondary outcomes after the first DAIR: sepsis, cellulitis, postoperative infection, endocarditis, amputation, knee fusion, resection, drainage, arthrotomy, and debridement. To answer our first and second study questions, we used frequency testing from the available AJRR data. Because of competing risks and issues with incomplete data, we used the cumulative incidence function to evaluate the outcomes specific to study question 3. Results Of the patients who underwent DAIR, 93% (5406 of 5827) had one DAIR and 8% (421 of 5827) had more than one. Among the DAIR population, at least 35% of TKAs and 38% of THAs were identified as having experienced an additional PJI-related event (an additional surgical procedure on the same joint, sustained an infectious endpoint in the linked CMS-AJRR dataset, or they had died). The cumulative incidence of developing a further medical or surgical condition related to the joint that had the initial DAIR were as follows: 48% (95% CI 42% to 54%) at 8 years after a DAIR following a TKA and 42% (95% CI 37% to 46%) at 4 years after a DAIR following a THA. The timepoints for TKA and THA are different because there are more longitudinal procedure data available for TKAs regarding DAIR procedures than for THAs. Conclusion In this study, we used data from the AJRR to assess the incidences of single and multiple DAIR attempts and additional surgical- and infection-related sequalae. Continued investigation is required to determine the fate of infected joints that undergo DAIR with regard to ultimate patient outcome. Future cross-sectional studies using large datasets are necessary to assess functional outcomes and determine the risk of persistent infection after DAIR more precisely. Level of Evidence Level III, therapeutic study.

AbstractBackgroundTrauma remains the leading cause of pediatric mortality in the United States. Although use of massive transfusion protocols (MTPs) in this population is widespread, optimal pediatric resuscitation is not well established. We sought to assess contemporary pediatric MTP practice in the United States.Study Design and MethodsA web‐based survey was designed by the Association for the Advancement of Blood & Biotherapies (AABB) Pediatric Transfusion Medicine Subsection and distributed to select American College of Surgeons (ACS) Level I Verified pediatric trauma centers. The survey assessed current MTP policy, implementation, and recent changes in practice.ResultsResponse rate was 55% (22/40). Almost half of the respondents were from the South. The median RBC:plasma ratio was 1 (interquartile range 1–1.5). Protocolized fibrinogen supplementation was common while integration of antifibrinolytic therapy into MTPs was infrequent. Viscoelastic testing (VET) was available at most sites, 71% (15/21, one site did not respond), and was generally utilized on an ad‐hoc basis. Roughly, a third of sites had changed their MTP in the past 3 years due to blood supply issues, and about a third reported having group O Whole Blood on‐site.ConclusionMTP practice is similar throughout the United States. Though fibrinogen supplementation is common—other emerging interventions such as antifibrinolytic therapy or utilization of routine viscoelastic testing—are not widespread. Pediatric transfusion medicine experts must continue to follow practice change, as contemporary large trials begin to characterize new supportive modalities to optimize resuscitation in pediatric trauma patients.

AbstractINTRODUCTIONCardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTLD).METHODSTwo hundred forty‐seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) and 189 non‐carrier controls completed baseline LS7, and longitudinal neuroimaging and neuropsychological testing.RESULTSAmong variant carriers, higher baseline LS7 is associated with slower accumulation of frontal white matter hyperintensities (WMHs), as well as slower memory and language declines. Higher baseline LS7 associated with larger baseline frontotemporal volume, but not frontotemporal volume trajectories.DISCUSSIONBetter baseline cardiovascular health related to slower cognitive decline and accumulation of frontal WMHs in autosomal dominant FTLD. Optimizing cardiovascular health may be an important modifiable approach to bolster cognitive health and brain integrity in FTLD.Highlights Better cardiovascular health associates with slower cognitive decline in frontotemporal lobar degeneration (FTLD). Lifestyle relates to the accumulation of frontal white matter hyperintensities in FTLD. More optimal cardiovascular health associates with greater baseline frontotemporal lobe volume. Optimized cardiovascular health relates to more favorable outcomes in genetic dementia.

Abstract Nicotine exposure in the context of smoking or vaping worsens airway function. Although nicotinic acetylcholine receptors (nAChRs) are commonly thought to exert effects through the peripheral nervous system, we previously showed that airway smooth muscle (ASM) expresses them, particularly α7 subtype nAChR (α7nAChR), with functional effects on contractility and metabolism. However, the mechanisms of nAChR regulation and downstream effects in ASM are not fully understood. Using ASM cells from people without asthma versus people with mild to moderate asthma, we tested the hypothesis that nAChR-specific endoplasmic reticulum (ER) chaperones, resistance to inhibitors of cholinesterase 3 (RIC-3) and transmembrane protein 35A (TMEM35A) promote cell surface localization of α7nAChR with downstream influence on its functionality: effects exacerbated by inflammation. We found that mild to moderate asthma and exposure to proinflammatory cytokines relevant to asthma promote chaperone and α7nAChR expression in ASM. Downstream, ER stress was linked to nicotine/α7nAChR signaling, where RIC-3 and TMEM35 regulate nicotine-induced ER stress, intracellular Ca2+ regulation, and ASM cell proliferation. Overall, our data highlight the importance α7nAChR chaperones in mediating and modulating nicotine effects in ASM toward airway contractility and remodeling.

Abstract Introduction: Current guidelines state the effectiveness of desmopressin to reduce hematoma expansion in antiplatelet-related intracerebral hemorrhage (ICH) is uncertain. This study sought to determine if desmopressin decreased hematoma expansion in ICH patients on antiplatelet agents. Methods: We conducted a multi-center, retrospective propensity-matched cohort study at 11 US emergency departments (ED) that participate in EMPHARM-NET. Adult patients ≥18 years with a primary diagnosis of spontaneous ICH on antiplatelets prior to admission from January 1, 2017 through May 1, 2021 were included. The primary endpoint was good or excellent hemostatic efficacy within the first 24 hours following ICH between patients that did and did not receive desmopressin. Brain imaging was reviewed using 3D-Slicer by blinded expert physicians. Results: Overall, 1408 patients were evaluated for inclusion. A total of 324 patients were included, of which 13.8% (n=45) received desmopressin and 86.1% (n=279) did not. After propensity matching, 35 patients receive desmopressin compared to 140 controls. Baseline hematoma volume (27.6 mL vs. 2.1 mL) and was significantly higher in the desmopressin group. The primary endpoint of good or excellent hemostatic efficacy was similar between groups (74.3% desmopressin group vs. 85% control group, -10.7% [-28.1% to 6.7%]). There was no difference in secondary outcomes. Conclusion: In this multicenter cohort, patients receiving desmopressin had higher baseline intraparenchymal hematoma volume, and did not appear to result in improved hemostatic efficacy relative to the control group. These results suggest against routine administration of desmopressin for antiplatelet-related ICH, though future study in a randomized trial design is necessary.

AbstractBackgroundIrritable bowel syndrome (IBS) is a disorder of gut–brain interaction characterized by abdominal pain and altered bowel habits, with patient‐perceived dissatisfaction of treatment symptom control. We assessed disease burden, satisfaction with medication use, and impact on activities, in participants with IBS with constipation (IBS‐C) and diarrhea (IBS‐D).MethodsThis study assessed data from a large, United States survey of adults querying demographics, comorbid conditions, quality of life, medication use, satisfaction with symptom control, and work productivity. Participants were grouped into the IBS‐C or IBS‐D cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported.Key ResultsNine hundred and ten participants with IBS‐C and 669 with IBS‐D were matched to controls. The most reported symptoms were abdominal discomfort for IBS‐C and abdominal pain and abdominal discomfort for IBS‐D. Among the IBS‐C and IBS‐D cohorts, 74.2% and 65.9%, respectively, took prescription and/or over‐the‐counter medication for their symptoms. Respondents were more dissatisfied than satisfied with control of their symptoms. Respondents taking prescription medication(s) with or without over‐the‐counter medication(s) reported better symptom control than respondents only taking over‐the‐counter medications (p < 0.001). There was significantly higher mean presenteeism, work productivity loss, and daily activity impairment (p < 0.001 for all) in respondents with IBS compared with controls.Conclusions and InferencesThis study provides insight into respondents' experiences of IBS symptoms, including the impact on daily activity, as well as satisfaction with control of symptoms and prescription and over‐the‐counter medications.

AimTransbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease‐associated ILD (CTD–ILD) in cryobiopsies.MethodsWe examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)‐established CTD–ILD and compared them to a prior series of 121 biopsies from patients with MDD‐established IPF or FHP.ResultsA non‐specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD–ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD–ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD–ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD–ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD–ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD–ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD–ILD over IPF, but were infrequent.ConclusionsIn the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD–ILD in a cryobiopsy, but CTD–ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

ImportanceAsymmetric oropharynx uptake on positron emission tomography (PET)/computed tomography (CT) is a common incidental finding and often prompts otolaryngology referral to rule out malignancy; however, the true risk of malignancy based on this finding is unknown.ObjectiveTo identify the incidence of oropharynx cancer in patients with incidental asymmetric oropharynx PET uptake.Design, Setting, and ParticipantsIn this retrospective cohort study, patients 18 years and older undergoing PET/CT scans at Mayo Clinic between January 2001 and December 2018 were included. Patients with a history or pretest suspicion of oropharynx cancer were excluded. Data were analyzed from March 2021 to December 2023.ExposureBlinded radiologic review of imaging studies, including measurement of maximum standardized uptake values (SUVmax) of the ipsilateral side of concern and contralateral side. Retrospective medical record review for associated clinical data.Main Outcomes and MeasuresThe primary study outcome was the incidence of oropharynx cancer diagnosis in patients with asymmetric oropharynx PET uptake. The primary outcome was formulated before data collection.ResultsOf the 1854 patients identified with asymmetric oropharynx PET uptake, 327 (17.6%) met inclusion criteria. Of these, 173 (52.9%) were male, and the median (range) age was 65.0 (24.8-90.7) years. The mean (SD) follow-up interval was 52.1 (43.4) months. A total of 18 of 327 patients (5.5%) were newly diagnosed with oropharynx cancer. The most common diagnosis was squamous cell carcinoma (n = 9), followed by lymphoma (n = 8), and sarcoma (n = 1). Patients with an incidental diagnosis of oropharynx cancer had higher mean (SD) ipsilateral SUVmax (8.7 [3.7] vs 5.3 [1.9]) and SUVmax ratio (3.0 [1.6] vs 1.6 [0.6]) compared with patients with normal examination findings. SUVmax ratio and difference were found to be good discriminators of oropharynx cancer, with areas under the receiver operating characteristic curve of 86.3% (95% CI, 76.4-94.6) and 85.8% (95% CI, 74.8-94.6), respectively. Patients with a new diagnosis of oropharynx cancer were more likely to have a corresponding CT abnormality than those with normal examination findings (6 of 18 [33%] vs 24 of 295 [8.1%]). Patients with concerning lesions on oropharynx palpation by an otolaryngology health care professional were significantly more likely to be diagnosed with oropharynx cancer compared with patients with normal examination findings (odds ratio, 28.4; 95% CI, 6.6-145.8).Conclusions and RelevanceIn this cohort study, while incidental asymmetric oropharynx PET uptake was common, a new diagnosis of oropharynx cancer was not and potentially results in a large volume of unnecessary referrals and work-up. Using SUVmax ratio, SUVmax difference, and CT correlation may increase the benefit of referral. Patients with a palpable oropharynx lesion and asymmetric oropharynx PET uptake should undergo confirmatory biopsy.