Faculty Bibliography

OBJECTIVE:Low placentation is associated with increased risk of postpartum hemorrhage (PPH). There is a paucity of data on the association between second trimester low placentation that later resolves, and PPH. Our objective was to investigate the association of resolved low placentation and other prenatal ultrasound markers, and PPH with delivery. STUDY DESIGN/METHODS:This was a retrospective matched case-control (1:1) study of full term, singleton pregnancies complicated by PPH who delivered vaginally at our academic center between 2018-2022. All patients received a transvaginal ultrasound in the second and third trimester. PPH was defined as quantitative blood loss (QBL) >1L within 24 hours of delivery. Primary exposure variable was second-trimester low placentation (defined as previa or low-lying placenta within 10mm from internal os) that resolved before labor. Additional exposure variables included uterine leiomyoma, first-trimester subchorionic hematoma, second-trimester cervical length< 25mm, and third-trimester polyhydramnios or large for gestational age (LGA) fetus. Chi-square test and unpaired student t-test were used to compare categorical and continuous variables, respectively. Multivariable logistic regression analysis was performed to adjust for confounders. RESULTS:We compared 400 gravidas with PPH to 400 without. Gravidas were matched by age, parity, gestational age and mode of vaginal delivery. PPH occurred more often in cases with resolved previa versus controls (12 % vs 4.6 %, p < 0.01). On multivariate analysis, those with resolved previa were 2.58 times more likely to have PPH, compared to controls (aOR 2.58, 95% CI 1.49 - 4.81, p < 0.001). PPH rates were also increased in those with leiomyoma (aOR 3.50, 95% CI 1.59 - 7.72, p = 0.002). Rates of subchorionic hematoma, short cervical length, polyhydramnios and LGA fetus were similar between groups. CONCLUSION/CONCLUSIONS:Low placentation on second-trimester ultrasound is associated with an increased risk of PPH, even when it appears to resolve in the third trimester. Routine assessment of placentation in the second trimester should be considered to improve prediction and management of PPH.

The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.4% female) in the Millennium Cohort Study (N = 10,647). Survey weights were used to account for attrition. At each timepoint, past month alcohol use frequency was self-reported, parents and cohort members reported internalizing/externalizing symptoms using the Strengths and Difficulties Questionnaire. We controlled for alcohol expectancies, sex, and four cumulative risk indices (perinatal risk, early childhood adverse parenting, longitudinal parent-level risk occurrence, and persistent household socioeconomic deprivation). More frequent past month alcohol use at age 11 predicted increased internalizing symptoms at age 14 (β = 0.06; p =.01). More frequent past month alcohol use at age 14 predicted increased externalizing symptoms at age 17 (β = 0.11; p <.001). Increased internalizing symptoms consistently predicted reduced alcohol use at the next timepoint throughout the study period (11 years: β= -0.04; p =.03; 14 years: β= -0.09; p <.001). Increased externalizing symptoms at age 11 predicted increased alcohol consumption at age 14 (β = 0.06; p =.004). Frequent adolescent alcohol consumption represents a significant risk for subsequent mental health difficulties. Externalizing symptoms and alcohol use frequency appear to exacerbate one another. Internalizing symptoms may reduce the risk of frequent alcohol consumption. Incorporating routine alcohol screening into adolescent mental health treatment settings could reduce the risk of comorbid externalizing and alcohol use disorders.

PURPOSE/OBJECTIVE:To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery. BACKGROUND:Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC. METHODS:International multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated. RESULTS:=0.96) involvement. CONCLUSIONS:Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared to upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

BACKGROUND:To improve outcomes for patients with pancreatic ductal adenocarcinoma, a complete resection is crucial. However, evidence regarding the impact of microscopically positive surgical margins (R1) on recurrence is conflicting due to varying definitions and limited populations of patients with borderline-resectable and locally advanced pancreatic cancer. Therefore, we aimed to determine the impact of the resection margin status on recurrence and survival in patients with pancreatic ductal adenocarcinoma stratified by local tumor stage. METHODS:We performed a retrospective cohort study on patients with nonmetastatic pancreatic ductal adenocarcinoma undergoing pancreatectomy at a high-volume academic center (2012-2022). R1 was subclassified into microscopic invasion of the margin (R1 direct) or carcinoma present within 1 mm but not directly involving the margin (R1 <1 mm). Overall survival and time to recurrence were assessed by log-rank test and multivariable Cox regression. RESULTS:Of 472 included patients, 154 (33%) had an R1 resection. Of those 50 (32%) had R1 <1 mm and 104 (68%) R1 direct. The most commonly involved margin was the uncinate (41%) followed by the pancreatic neck (16%) and vascular margins (9%). Overall, a stepwise shortening of time to recurrence and overall survival was observed with an increasing degree of margin involvement (median time to recurrence: R0 39.3 months, R1 <1 mm 16.0 months, and R1 direct 13.4 months, all comparisons P < .05). Multivariable analyses confirmed the independent prognostic value of R1 direct across all surgical stages. CONCLUSION/CONCLUSIONS:The resection margin status portends an independent prognostic value. Moreover, this association persists in patients with borderline-resectable and locally advanced pancreatic cancer. Increasing the R0-resection rate is the most important potentially influenceable prognostic factor for improving surgery-related outcomes.

IMPORTANCE/UNASSIGNED:Among older adults with ischemic heart disease, participation in traditional ambulatory cardiac rehabilitation (CR) remains low. While mobile health CR (mHealth-CR) provides a novel opportunity to deliver care, age-specific impairments to technology use may limit uptake, and efficacy data are currently lacking. OBJECTIVE/UNASSIGNED:To test whether mHealth-CR improves functional capacity in older adults. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The RESILIENT phase 2, multicenter, randomized clinical trial recruited patients aged 65 years or older with ischemic heart disease (defined as a hospital visit for myocardial infarction or coronary revascularization) from 5 academic hospitals in New York, Connecticut, and Massachusetts between January 9, 2020, and April 22, 2024. INTERVENTION/UNASSIGNED:Participants were randomized 3:1 to mHealth-CR or usual care. mHealth-CR consisted of commercially available software delivered on a tablet computer, coupled with remote monitoring and weekly exercise therapist telephone calls, delivered over a 3-month duration. As RESILIENT was a trial conducted in a routine care setting to inform decision-making, participants in both arms were also allowed to receive traditional CR at their cardiologist's discretion. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was change from baseline to 3 months in functional capacity, measured by 6-minute walk distance (6MWD). Secondary outcomes were health status (12-Item Short Form Health Survey [SF-12]), residual angina, and impairment in activities of daily living. RESULTS/UNASSIGNED:A total of 400 participants (median age, 71.0 years [range, 65.0-91.0 years]; 291 [72.8%] male) were randomized to mHealth-CR (n = 298) or usual care (n = 102) and included in the intention-to-treat analysis. Of those, 356 participants (89.0%) returned in person for 6MWD assessment at 3 months. For the primary outcome, there was no adjusted difference in 6MWD between participants receiving mHealth-CR vs usual care (15.6 m; 95% CI, -0.3 to 31.5 m; P = .06). Among subgroups, there was an improvement in 6MWD among women (36.6 m; 95% CI, 8.7-64.4 m). There were no differences in any secondary outcomes between groups (eg, adjusted difference in SF-12 physical component scores at 3 months: -1.9 points; 95% CI, -3.9 to 0.2 points). Based on inverse propensity score weighting, there was no effect of mHealth-CR on 6MWD among those who did not attend traditional CR (25.7 m; 95% CI, -8.7 to 60.2 m). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of mHealth-CR vs usual care, mHealth-CR did not significantly increase 6MWD or result in improvements in secondary outcomes. The findings suggest the older adult population may require more age-tailored mHealth strategies to effectively improve outcomes. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03978130.

Nonalcoholic fatty liver disease (NAFLD) and its development into nonalcoholic steatohepatitis (NASH) are challenging health concerns globally. Clinically, the prevalence and severity of NAFLD/NASH are higher in men than in premenopausal women. NAFLD is strongly correlated with obesity, both of which are tied to high-fat/fructose-rich western diets. Therefore, we aimed to investigate sexual dimorphism in NAFLD pathogenesis in male and female C57BL/6 mice fed different diets. Male and female C57BL/67 mice were divided into four groups and kept on a chow (C), chow plus high fructose (CF), high fat (HF), and high fat plus high fructose (HFF) diet for 22 weeks. Liver tissues were collected at the end of the study and processed for NAFLD/NASH-related histology (H&E and trichrome staining), protein expression (SREBP1, SCAP, FABP4, α-SMA, TGF-β and L-PGDS), and biochemical parameters measurement. Our results displayed that female mice exhibited protection against NAFLD and diabesity on HF and HFF diets compared to male mice fed similar diets. Additionally, female mice showed protection from fibrosis compared to male mice. Both male and female mice fed HF and HFF diet groups displayed the cytosol-to-nuclear translocation of Lipocalin Prostaglandin D₂ Synthase (L-PGDS). Cytoplasmic levels of L-PGDS were absent in females compared to low levels in males, revealing a possible sex-specific mechanism tied to fructose and fat metabolism. Collectively, female mice showed protection against NAFLD and diabesity relative to male mice, accompanied by differential regulation of hepatic lipocalin prostaglandin D₂ synthase.

BACKGROUND:Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. METHODS:We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. RESULTS:We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. CONCLUSIONS:Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. LEVEL OF EVIDENCE/METHODS:Level 2, Diagnostic Tests or Criteria.

BACKGROUND:RYGB consists of the Roux limb (RL), the biliopancreatic limb (BPL), and the common channel (CC). There is no consensus on the optimal limb lengths. METHODS:Using a mouse model of RYGB, 30 diet-induced obese mice were divided into two groups with varying BPL and CC lengths: a standard BPL with a long CC (RYGB S) and a long BPL with a short CC (RYGB L). Additionally, 9 age-matched, lean control mice (LC) were also included in this study. RESULTS:RYGB S had limb lengths of RL = 17%, BPL = 24%, and CC = 59%. RYGB L had limb lengths of RL = 17%, BPL = 32%, and CC = 51%. RYGB S and RYGB L had 67% and 40% survival, respectively. Mortality in RYGB L included more instances where the cause of death was not apparent. RYGB L demonstrated greater weight loss, lower energy expenditure, and lower heart mass as compared to RYGB S. Both RYGB groups had lower epidydimal fat mass, spleen mass, and bone mineral density compared to LC. RYGB L had a lower heart mass than RYGB S and LC. While the relative abundance of Eubacterium was lower in RYGB L than in RYGB S, no other gut microbiota differences were observed. CONCLUSIONS:A longer BPL with a shorter CC induces greater weight loss but may lead to adverse effects, including lower heart mass, reduced bone density, and deaths with unclear causes.

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.