Citations

AbstractIntroductionSmoking commercial tobacco products is highly prevalent in American Indian and Alaska Native (Indigenous) pregnancies. This disparity directly contributes to maternal and fetal mortality. Our objective was to describe cigarette smoking prevalence, cessation intervention uptake, and cessation behaviors of pregnant Indigenous people compared to sex and age-matched regional cohort.Aims and MethodsPregnancies from an Indigenous cohort in Olmsted County, Minnesota, identified in the Rochester Epidemiology Project, were compared to pregnancies identified in a sex and age-matched non-Indigenous cohort from 2006 to 2019. Smoking status was defined as current, former, or never. All pregnancies were reviewed to identify cessation interventions and cessation events. The primary outcome was smoking prevalence during pregnancy, with secondary outcomes measuring uptake of smoking cessation interventions and cessation.ResultsThe Indigenous cohort included 57 people with 81 pregnancies, compared to 226 non-Indigenous people with 358 pregnancies. Smoking was identified during 45.7% of Indigenous pregnancies versus 11.2% of non-Indigenous pregnancies (RR: 3.25, 95% CI = 1.98–5.31, p ≤ .0001). Although there was no difference in uptake of cessation interventions between cohorts, smoking cessation was significantly less likely during Indigenous pregnancies compared to non-Indigenous pregnancies (OR: 0.23, 95% CI = 0.07–0.72, p = .012).ConclusionsIndigenous pregnant people in Olmsted County, Minnesota were more than three times as likely to smoke cigarettes during pregnancy compared to the non-indigenous cohort. Despite equivalent uptake of cessation interventions, Indigenous people were less likely to quit than non-Indigenous people. Understanding why conventional smoking cessation interventions were ineffective at promoting cessation during pregnancy among Indigenous women warrants further study.ImplicationsIndigenous pregnant people in Olmsted County, Minnesota, were greater than three times more likely to smoke during pregnancy compared to a regional age matched non-Indigenous cohort. Although Indigenous and non-Indigenous pregnant people had equivalent uptake of cessation interventions offered during pregnancy, Indigenous people were significantly less likely to quit smoking before fetal delivery. This disparity in the effectiveness of standard of care interventions highlights the need for further study to understand barriers to cessation in pregnant Indigenous people.

Abstract Background Pregnancy related cardiomyopathy is a significant cause of maternal morbidity and mortality globally. A presumed overlap between normal pregnancy-associated symptoms and clinical symptoms of cardiomyopathy contributes to delays in diagnosis and increased risk of maternal mortality. Purpose We sought to evaluate the association between patient-reported cardiovascular symptoms and the presence of cardiomyopathy among pregnant and postpartum patients. We hypothesize that individual cardiovascular symptoms are unrelated to the presence of cardiomyopathy. We also evaluated the use of a novel adaptation of a validated health status questionnaire in relation to cardiomyopathy. Methods We enrolled 48 pregnant (>13 weeks) and postpartum (up to 12 months) participants in a prospective study between October 2021 and February 2022. All study participants completed a baseline questionnaire, which included current cardiovascular symptoms, an assessment of health status using an adapted version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), followed by a resting transthoracic echocardiogram on the same day. We defined cardiomyopathy as a left ventricular ejection fraction (LVEF) <50% based on 2-D echocardiography. Fisher's exact and Wilcoxon rank-sum tests were employed to evaluate the association between reported cardiovascular symptoms, the adapted KCCQ-12 (KCC-A) score, and cardiomyopathy. Results At the time of enrollment, 67% were pregnant and 33% postpartum. Forty-eight percent identified as White, 31% as Black, 10% as Asian, and 10% as other race. The median age was 31 years (Q1: 28, Q3: 35) and 6% had an LVEF <50%. We found no statistically significant association between four reported cardiovascular symptoms (shortness of breath, orthopnea, fast breathing, and episodes of “asthma” that did not improve with inhalers or other treatment) and cardiomyopathy or medial E/e' ratio. KCC-A scores were low in the study population overall (median 52; Q1:40, Q3: 61). We demonstrated a significantly lower KCC-A score among women with LVEF <50% (median 24; Q1: 15, Q3: 44) compared to women with LVEF ≥50% (median 54; Q1: 44, Q3: 61) p=0.02. Conclusions We showed no significant association between individual cardiovascular symptoms and cardiomyopathy in an obstetric population. However, we demonstrate for the first time that an adapted KCCQ-12 questionnaire for health status assessment could potentially identify women with a high-likelihood of cardiomyopathy during the peripartum period who may benefit from additional evaluation including echocardiography. Larger studies are needed to validate this finding. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This study was funded by a research grant from the Miami Heart Research Institute, Florida Heart Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

Maintenance therapy after autologous stem cell transplant (ASCT) in multiple myeloma (MM) is the standard treatment and recommended to be continued until disease progression. However, in the real world, patients discontinue treatment due to various reasons. We sought to determine the effect of early versus late discontinuation on survival outcomes in MM patients who underwent ASCT at The Ohio State University. We retrospectively reviewed 340 patients who underwent ASCT from 2005 to 2016 and received maintenance therapy for at least six months without progression. We compared the outcomes of patients who received maintenance for three years or less (early group) to the patients who continued maintenance beyond three years (late group). Lenalidomide (89%) and bortezomib (10%) were the most common agents used for maintenance chemotherapy. In Kaplan–Meier analysis, patients in the late group had prolonged progression-free (PFS) (p < 0.001) and overall survival (OS) (p < 0.001). The 5-year estimated OS in late group was 96% vs. 79% in the early group and 5-year PFS was 80% in late group vs. 50% in the early group. The most common reasons for discontinuation of maintenance in early group were adverse events (55.9%) and patient preference (22.5%). For the late group, it was disease progression (23.9%) and adverse events (14.3%). Fifty-five percent of patients in the late group were still on maintenance treatment at the last follow-up. Continuation of maintenance therapy was thus associated with improved outcomes, while adverse events prevented most patients from continuing treatment.

AbstractProsthetic valve endocarditis (PVE) remains a serious condition with a high mortality rate. Precise identification of the PVE-associated pathogen/s and their virulence is essential for successful therapy and patient survival. The commonly described PVE-associated pathogens are staphylococci, streptococci, and enterococci, with Staphylococcus aureus being the most frequently diagnosed species. Furthermore, multi-drug resistance pathogens are increasing in prevalence and continue to pose new challenges mandating a personalized approach. Blood cultures in combination with echocardiography are the most common methods to diagnose PVE, often being the only indication, it exists. In many cases, the diagnostic strategy recommended in the clinical guidelines does not identify the precise microbial agent, and frequently, false-negative blood cultures are reported. Despite the fact that blood culture findings are not always a good indicator of the actual PVE agent in the valve tissue, only a minority of re-operated prostheses are subjected to microbiological diagnostic evaluation. In this review, we focus on the diversity and the complete spectrum of PVE-associated bacterial, fungal, and viral pathogens in blood and prosthetic heart valve, their possible virulence potential, and their challenges in making a microbial diagnosis. We are curious to understand if the unacceptable high mortality of PVE is associated with the high number of negative microbial findings in connection with a possible PVE. Herein, we discuss the possibilities and limits of the diagnostic methods conventionally used and make recommendations for enhanced pathogen identification. We also show possible virulence factors of the most common PVE-associated pathogens and their clinical effects. Based on blood culture, molecular biological diagnostics, and specific valve examination, better derivations for the antibiotic therapy as well as possible preventive intervention can be established in the future.

Background Musculocontractural Ehlers−Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated. Methods We collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations. Results Sixty-six patients in 48 families (33 males/females; 0–59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype–phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE. Conclusion This first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.

Hepatic fibrosis is driven by deposition of matrix proteins following liver injury. Hepatic stellate cells (HSCs) drive fibrogenesis, producing matrix proteins, including procollagen I, which matures into collagen I following secretion. Disrupting intracellular procollagen processing and trafficking causes endoplasmic reticulum stress and stress‐induced HSC apoptosis and thus is an attractive antifibrotic strategy. We designed an immunofluorescence‐based small interfering RNA (siRNA) screen to identify procollagen I trafficking regulators, hypothesizing that these proteins could serve as antifibrotic targets. A targeted siRNA screen was performed using immunofluorescence to detect changes in intracellular procollagen I. Tumor necrosis factor receptor associated factor 2 and noncatalytic region of tyrosine kinase‐interacting kinase (TNIK) was identified and interrogated in vitro and in vivo using the TNIK kinase inhibitor NCB‐0846 or RNA interference‐mediated knockdown. Our siRNA screen identified nine genes whose knockdown promoted procollagen I retention, including the serine/threonine kinase TNIK. Genetic deletion or pharmacologic inhibition of TNIK through the small molecule inhibitor NCB‐0846 disrupted procollagen I trafficking and secretion without impacting procollagen I expression. To investigate the role of TNIK in liver fibrogenesis, we analyzed human and murine livers, finding elevated TNIK expression in human cirrhotic livers and increased TNIK expression and kinase activity in both fibrotic mouse livers and activated primary human HSCs. Finally, we tested whether inhibition of TNIK kinase activity could limit fibrogenesis in vivo. Mice receiving NCB‐0846 displayed reduced CCl4‐induced fibrogenesis compared to CCl4 alone, although α‐smooth muscle actin levels were unaltered. Conclusions: Our siRNA screen effectively identified TNIK as a key kinase involved in procollagen I trafficking in vitro and hepatic fibrogenesis in vivo.

IntroductionWe calculate the financial margins for delivery of routine antenatal care as reimbursed by Medicaid. Prenatal care cost varies with overhead, health care provider type, and number of office visits. Antenatal care is only one component of the global maternity bundle, which also includes intrapartum and postpartum care.MethodsTime for provision of low‐risk antenatal care was determined prospectively from a study of 133 low‐risk pregnant patients. Health care provider time cost was estimated using mean wages for obstetricians and midwives. Margins were estimated by subtracting cost of provider services and overhead for the antenatal component of maternity care from total Medicaid reimbursement for the pregnancy global package (CPT 59400) using 2015 dollars. The maternity bundle elements of routine prenatal laboratory tests, ultrasounds, intrapartum care, and postpartum care were not included in our analysis of cost components.ResultsPatients received an average of 215 minutes of direct provider time per pregnancy. At the 50th percentile for physician payment and assuming overhead is 53.4% of revenue, practice margins varied by state from −$1067 to +$675, with a median of −$357. Median margins for midwifery care were +$15, with a range of −$579 to +$885. Margins were negative if overhead costs exceeded 33% of revenue for physician care and 55% of revenue for midwifery care.DiscussionIn many states, Medicaid reimbursement for the global maternity package is less than the actual cost of antenatal care alone. Improving reimbursement or decreasing costs is necessary to make maternity care more cost‐effective.

8009 Background: Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses have been associated with better progression free survival (PFS) and overall survival (OS). Serum (SIFE) and urine immunofixation are the currently used markers for biochemical documentation of CR after which marrow is tested for plasma cell clearance. Next generation flow cytometry and sequencing are used to document the presence of minimal residual disease (MRD). Mass spectrometry of blood by MALDI (Mass-Fix) is a new simple, inexpensive, sensitive, and specific means of detecting monoclonal immunoglobulins. To better test the hypothesis that Mass-Fix is superior to existing methodologies to predict for survival outcomes—especially SIFE-- samples from the STAMINA trial (NCT01109004), a trial comparing 3 transplant approaches among patients who have already received induction, were employed. Methods: Five-hundred and seventy-five patients were included. Samples from enrollment post-induction (post-I) and 1-year post enrollment (1YR) were tested when available. Four response parameters were assessed univariately: Mass-Fix, SIFE, complete response, and MRD by next generation flow cytometry. Mass spectrometry spectra were evaluated in a blinded fashion. Complete response was according to the 2006 International Myeloma Working Group criteria. Multivariate Cox proportional hazard models using stepwise regression were developed to explore the independent effect of the different response parameters on PFS and OS and interactions with other risk factors. Results: Of the 4 response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses (Table). Of the 4 post-I measurements, only MRD predicted for PFS; however, Mass-Fix was the only post-I measurement to predict for OS. Of all the 1-year measures, both 1YR Mass-Fix and 1YR MRD positivity predicted for inferior PFS and OS. In models including MRD and Mass-Fix, SIFE and CR were not prognostic for PFS or OS. Conclusions: Mass-Fix is a powerful means to track monoclonal proteins. The full utility of Mass-Fix was not exploited given the absence of a diagnostic sample and the fact that only serum (and not urine) was tested. Despite these limitations, it performed well at pre-induction and at 1 year. Mass-Fix provides a convenient and non-invasive means of predicting for myeloma outcomes. Clinical trial information: NCT01109004. [Table: see text]

BackgroundSinusitis is a common outpatient diagnosis made by physicians and is a reason for referral to otolaryngologists. A foundation in basic sinonasal anatomy is critical in understanding sinus pathophysiology and avoiding complications. Our objective in this study was to develop and to validate a self‐directed surgical anatomy video for medical students.MethodsTwo multimedia videos were developed highlighting sinonasal anatomy. In Video 1 we included audio narration and radiologic imaging. Video 2 incorporated highlighted images from a sinus surgery video. An assessment was developed to test sinonasal anatomy landmarks, spatial recognition of structures, and their clinical relevance. An expert panel of rhinologists scored face and content validity of the curriculum videos and assessment. Factor analysis was used to separate questions into face and content validity domains, and a one‐sample t test was performed.ResultsThe panel scored face validity (Videos 1 and 2: 4.4/5) and content validity (Video 1: 4.5/5, 0.83; Video 2: 4.3/5, 0.75) significantly higher than a neutral response. There were no statistical differences for face or content validity between videos. The assessment was rated suitable (29%) or very suitable (57%) for testing basic sinonasal surgical anatomy, and the majority (71%) of respondents agreed (14%) or strongly agreed (57%) that the assessment thoroughly covered the sinus anatomy content with which medical students should be familiar.ConclusionWe have developed two videos and an assessment that highlight and test sinonasal anatomy. Future studies will aim to identify whether the use of a self‐directed video curriculum improves sinonasal anatomy awareness and whether incorporation of surgical endoscopic videos augments training.