Faculty Bibliography
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school:LISOM
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13740
Hemorrhagic placental lesions on ultrasound: a continuum of placental abruption
Placental abruption has classically been defined as the premature separation of a normally located placenta before delivery of the fetus. Traditionally, this diagnosis was based on clinical symptoms, including vaginal bleeding, pain, and fetal distress. This definition, however, preceded the advent of obstetric ultrasound. Ultrasound frequently identifies various hemorrhagic lesions, such as retroplacental, subchorionic, intraamniotic, intraplacental, and preplacental hematomas in both symptomatic and asymptomatic patients. These variable ultrasound findings lead to new challenges as to what to define as an abruption, particularly in the absence of symptoms. This ambiguity in defining placental abruption affects clinical decision-making and hinders our understanding of the pathophysiology of abruption, presenting challenges in studying abruption. It is likely that these varying sonographic findings may precede the classic presentation of vaginal bleeding and pain and therefore are often concealed abruptions. This commentary highlights the importance of developing clear diagnostic guidelines for placental abruption, given its association with severe outcomes including a high rate of perinatal mortality and maternal morbidity. We aim to elucidate the complexities of ultrasound diagnosis in placental abruption, advocating for precise criteria to better guide clinical practice. We propose that these ultrasound findings of hemorrhagic placental lesions after 20 weeks of gestation in asymptomatic patients should be considered part of the spectrum of abruption, while in symptomatic patients should be taken as confirmation of the diagnosis of abruption.
PMID: 40312868
ISSN: 1619-3997
CID: 5834342
Belzutifan-Associated Hypoxia: A Review of the Novel Therapeutic, Proposed Mechanisms of Hypoxia, and Management Recommendations
Belzutifan is a hypoxia-inducible factor-2α (HIF-2α) inhibitor that received FDA approval in 2021 for treating cancers resulting from von Hippel-Lindau (VHL) disease, including clear cell renal cell carcinoma (ccRCC), followed by approval in 2023 for sporadic ccRCC that has progressed through multiple lines of therapy. HIF-2α is a promising drug target, as VHL is commonly inactivated in ccRCC, which results in HIF-2α-mediated signaling that is considered central to tumorigenesis. Belzutifan has demonstrated efficacy in clinical trials in the first-line and subsequent line settings, and in combination with tyrosine kinase inhibitors. Despite being overall well tolerated, belzutifan has a distinct safety profile because of its unique mechanism of action. Anemia was the most common adverse event observed in clinical trials and is considered an on-target effect. Hypoxia is also frequently observed and commonly results in dose reductions, treatment discontinuation, and supplemental oxygen use. This review summarizes the rates of hypoxia seen in clinical trials of belzutifan in ccRCC. As the cause of hypoxia is not well understood, this review also discusses possible mechanisms of hypoxia based on preclinical studies of the HIF pathway and HIF-2α inhibitors. Finally, this review proposes monitoring and management recommendations for clinicians prescribing belzutifan to ccRCC patients.
PMCID:12346180
PMID: 40806229
ISSN: 1422-0067
CID: 5907492
Statement from the frontal fibrosing alopecia international expert alliance: SOFFIA 2024
BACKGROUND:As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA. OBJECTIVE:To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA. METHODS:Sixty-nine hair experts from six continents were invited to participate in a three-round Delphi process. The final stage was held as a virtual meeting facilitated via Zoom. The consensus threshold was set at ≥66%. RESULTS:Of 365 questions, expert consensus was achieved in 204 (56%) questions following completion of the three rounds. Three additional questions were included at the final meeting. The category with the strongest consensus agreement was disease monitoring (9; 100%). Questions pertaining to physical therapies achieved the least category consensus (15; 40%), followed by systemic therapy (45; 43%). LIMITATIONS/CONCLUSIONS:The study lacked sufficient representation from Africa and South America. CONCLUSION/CONCLUSIONS:SOFFIA highlights areas of agreement and disagreement among experts. Robust research is warranted to provide evidence-based treatment recommendations.
PMID: 40698981
ISSN: 1468-3083
CID: 5901552
Long-COVID incidence proportion in adults and children between 2020 and 2024
BACKGROUND:Incidence estimates of post-acute sequelae of SARS-CoV-2 infection, also known as long-COVID, have varied across studies and changed over time. We estimated long-COVID incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes). METHODS:This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and two control groups-- contemporary COVID-19 negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long-COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative (N3C), National Patient-Centered Clinical Research Network (PCORnet), and PEDSnet) implemented its own long-COVID definition. We introduced a harmonized definition for adults in a supplementary analysis. RESULTS:Overall, 4% of children and 10-26% of adults developed long-COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5-6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants. CONCLUSION/CONCLUSIONS:Our findings indicate that preventing and mitigating long-COVID remains a public health priority. Examining temporal patterns and risk factors of long-COVID incidence informs our understanding of etiology and can improve prevention and management.
PMID: 39907495
ISSN: 1537-6591
CID: 5783962
Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease
BACKGROUND:Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. RESULTS:We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14). CONCLUSIONS:Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease.
PMCID:12273372
PMID: 40676597
ISSN: 1474-760x
CID: 5897492
Satellitosis/in-transit metastasis in cutaneous squamous cell carcinoma: Risk factors and the prognostic significance
BACKGROUND:Satellitosis or in-transit metastasis (S-ITM) from cutaneous squamous cell carcinoma (cSCC) is associated with poor outcomes but is not included in current staging guidelines. OBJECTIVE:To determine risk factors and prognostic significance of S-ITM. METHODS:This cohort study included 8,901 patients with cSCC from 12 institutions (1998-2023). Risk factors for S-ITM were calculated using logistic regression. Outcomes were compared with 1:2 propensity score matched controls using a Fine-Gray subdistribution hazard model. RESULTS:Seventy-seven patients developed S-ITM. Increased patient age (OR 1.03, 95% CI 1.01-1.05, p<0.01), history of immunosuppression (OR 4.31, 95% CI 2.59-7.10, p<0.001), higher BWH stage (T2a OR 4.14, 95% CI 2.05-8.41; T2b OR 15.96, 95% CI 8.58-31.19; T3 OR 30.27, 95% CI 10.70-79.04, all p<0.001) and LVI (OR 4.57, 95% CI 1.80-10.38, p=0.001) were independent risk factors for S-ITM. S-ITM was associated with LR (SHR 2.40, 95% CI 1.43-4.04, p<0.001), NM (SHR 1.89 (95% CI .02-3.49, p=0.04), DM (SHR 4.41, 95% CI 1.45-13.27, p=0.01), and DSD (SHR 4.48, 95% CI 2.34-8.58, p<0.001). LIMITATIONS/CONCLUSIONS:Retrospective cohort study. The rarity of S-ITM may limit statistical power. CONCLUSION/CONCLUSIONS:Patients with cSCC and S-ITM are at higher risk for poor outcomes independent of patient, tumor, and treatment characteristics.
PMID: 40683360
ISSN: 1097-6787
CID: 5897702
A systematic review of histological characteristics in arterial and venous thrombi
INTRODUCTION/UNASSIGNED:Despite being the leading causes of morbidity and mortality worldwide, very little is known about the similarities and differences between venous and arterial thrombi. This review is focused on comparing their structural, molecular, and temporal characteristics. METHODS/UNASSIGNED:from animal studies and humans were included. Data on structural components and temporal changes of thrombi were collected and analyzed. RESULTS/UNASSIGNED:There were 76 articles found eligible from the full-text review. Only two studies had simultaneous temporal and spatial comparisons and did not attempt to compare the two types of thrombi: arterial and venous. Therefore, comparative insights were additionally drawn from studies analyzing one thrombus type in isolation. Four common factors were identified: red blood cells (RBCs), white blood cells (WBCs), platelets, and fibrin. Platelet concentration was higher in arterial thrombi, while more red blood cells (RBCs) were found in the venous thrombi. CONCLUSIONS/UNASSIGNED:There is a clear lack of direct comparison between arterial and venous thrombi, with limited information on their evaluations. Most available findings are derived from independently conducted analyses. REGISTRATION/UNASSIGNED:The protocol was registered on PROSPERO (registration ID: CRD420251003712).
PMID: 40657995
ISSN: 1747-4094
CID: 5896922
Exploring the role of quality of life in surgical decision making for patients undergoing pancreatectomy
INTRODUCTION/BACKGROUND:The influence of baseline health-related quality of life (HRQoL) on peri-operative outcomes in pancreatobiliary (PB) patients is not well established. This study investigated the impact of baseline HRQoL on peri-operative outcomes and the effect of surgery on HRQoL. METHODS:A secondary post-hoc analysis of a multicenter trial (2011-2016) assessed PB patients undergoing pancreatectomy. Pre-operative and 30-day post-operative FACT-G surveys were analyzed. Logistic regressions determined associations between baseline HRQoL scores and 60-day major complications. Subgroup analysis evaluated change in HRQoL (pre-operative to 30-day scores). RESULTS:Among 391 patients, higher baseline HRQoL (FACT-G overall OR 0.54,p = 0.04) was associated with decreased likelihood of developing major complications. Surgery resulted in improvement in HRQoL for patients with chronic pancreatitis (10.2 points) compared to other pathologies (-7 to 3.9 points). CONCLUSION/CONCLUSIONS:Baseline HRQoL was associated with post-operative complications and HRQoL significantly improved for patients with chronic pancreatitis, highlighting the importance of HRQoL on patient-centered outcomes.
PMID: 40706119
ISSN: 1879-1883
CID: 5901802
Clinical journal of the American Society of Nephrology : CJASN. 2025:20(9):1247-1258.DOI: 10.2215/CJN.0000000775
Fall Risk in Maintenance Hemodialysis Patients: A Secondary Analysis of the HOPE Consortium Trial
BACKGROUND:Falls are thought to be common in patients undergoing maintenance hemodialysis, but little is known about their frequency or outcomes. In this prospective study, we sought to increase our knowledge regarding the incidence, timing, circumstances, and outcomes of falls in this population. METHODS:Between January 2021 and April 2023, adults undergoing maintenance hemodialysis from 103 U.S. dialysis facilities were enrolled in the HOPE Consortium trial, which randomized participants with moderate or severe chronic pain to a pain coping skills cognitive behavioral therapy intervention or usual care. Occurrence of falls was a pre-specified trial outcome. The research team inquired about falls at each four-week follow-up visit during the 36-week study. Multivariable regression was used to explore associations of demographic and clinical characteristics, including patient-reported symptoms, with fall risk. RESULTS:Of 643 trial participants, 178 (28%) experienced 293 falls over a cumulative follow-up period of 429 participant-years for an overall rate of 0.68 falls per participant-year (95% CI: 0.61, 0.76). Accidents were the most frequent cause of falls (38%). It was rare for falls to be related to the hemodialysis treatment or to occur in the hemodialysis unit. Of the 293 falls, 36 (12%) were evaluated in the emergency department without subsequent hospitalization, 41 (14%) resulted in a hospital admission, and 19 (7%) led to a fracture. In multivariable analyses, neither demographic characteristics severity of pain symptoms or medication use such as opioids at enrollment was associated with the fall risk. CONCLUSIONS:Falls were common in this cohort of maintenance hemodialysis patients with chronic pain, occurring in 28% of individuals during a planned follow-up of 36 weeks. Falls rarely occurred in the dialysis unit, with the vast majority occurring at participants' homes and due to accidental causes. There was no significant association between patient-reported symptoms or medication use and the risk of subsequent falls. TRIAL REGISTRATION/BACKGROUND:NCT04571619.
PMID: 40663732
ISSN: 1555-905x
CID: 5897102
Identifying Opportunities for Fluid Balance Optimization in Critically Ill Children
IntroductionFluid overload (FO), a state of pathologic positive cumulative fluid balance (CFB), is common in Pediatric Intensive Care Units (PICU) and associated with morbidity and mortality. Because different PICUs may have unique needs, barriers, and limitations to accurately report fluid balance (FB) and reduce FO, understanding the drivers of positive FB is needed. We hypothesize CFB >5% and >10% is common on ICU days 1 and 2, but that reasons for high %CFB will vary across sites, as will barriers to accurate FB recording and opportunities to improve FB recording/management.MethodsConcurrent mixed methods study utilizing a retrospective observational cohort design and prospective interview and survey design performed at four tertiary pediatric ICUs. FB data were extracted from the electronic health record. A federated data collection framework allowed for rapid data aggregation. The primary outcome was %CFB on ICU days 1 and 2, defined as total intake minus total output divided by ICU admission weight. Chi-square test and Wilcoxon rank sum tests compared results across and within sites.ResultsAmongst 3,071 ICU encounters, day 2 CFB >5% varied from 39% to 54% (p = 0.03) and day 2 CFB >10% varied from 16% to 25% (p = 0.04) across sites. Urine occurrence recordings and patients receiving >100% Holliday-Segar fluids on Day 1 differed across sites (p < 0.001). Sites discussed overall FB and specific FB goals on rounds with differing frequency (42-73% and 19-39%, respectively), but they reported similar barriers to accurate FB reporting and achievable opportunities to improve FB measurements, including patients/families not saving urine/stool, patients not tracking oral intake, and lack of standardized charting of flushes.ConclusionDay 2 CFB >5% and >10% was common among pediatric ICU encounters but proportion of patients varied significantly across ICUs. Individual ICUs have different drivers of FO that must be targeted to improve FB management.
PMID: 40665689
ISSN: 1525-1489
CID: 5897132
