Faculty Bibliography

BACKGROUND/UNASSIGNED:This study investigates the association between intra-operative balance and 2-year outcomes within subgroups defined by demographics and pre-operative joint balance. Our hypothesis is that patient demographics and the pre-operative state of the joint will impact patient sensitivity to post-operative balance and laxity and subsequent impact on outcome. METHODS/UNASSIGNED:A retrospective analysis of prospectively captured data across 5 sites with 5 surgeons was performed. All cases completed pre-operative demographics surveys, 2-year post-operative Knee Injury and Osteoarthritis Outcome Score (KOOS) and had a robot assisted total knee arthroplasty with an integrated digital joint balancing tool. Differences in associations between intra-operative final joint balance and 2-year KOOS pain outcomes in demographic and pre-operative balance subgroups were characterized. Associations informed clinically relevant thresholds to optimize TKA treatment for subgroups. RESULTS/UNASSIGNED:A total of 276 patients completed 2-year KOOS scores. Subgroups were defined from Sex, Age, BMI and pre-operative extension laxity. Men prefer a tight tolerance medially in extension and mid-flexion while females prefer a tight lateral flexion gap. Patients <70 years show a strong preference for equal rectangular gaps in extension, mid-flexion, and flexion, while older patients do not show a preference. Patients with BMI ≤30 demonstrate a preference for rectangular gaps, while patients with higher BMI do not. Finally, patients with looser pre-operative extension laxity (>3 mm) preferred a TKA with increased extension laxity compared to patients with minimal preoperative laxity. CONCLUSION/UNASSIGNED:Intraoperative differences in knee balance can influence patient outcome scores among different demographic groups at two years postoperatively. This suggests further research is warranted to determine how ligament balance and laxity may be optimized based on individual patient factors.

This comprehensive review examines the effects of various infections on pregnancy, focusing on maternal symptoms, fetal outcomes, diagnostic methods, and placental pathology. The paper covers bacterial, viral, and parasitic infections, their mechanisms of transmission, clinical presentations, and histopathologic findings in the placenta. It emphasizes the importance of early detection and intervention, highlighting the challenges in diagnosis due to often asymptomatic presentations. The review also discusses the placenta's role as a protective barrier and its immune defense mechanisms against pathogens. Overall, this paper serves as a comprehensive resource for understanding the complex interplay between maternal infections, placental pathology, and fetal outcomes.

Placental abruption is a complete or partial separation of the placenta from the uterine decidua. Clinical manifestations include vaginal bleeding, abdominal pain, uterine contractions, and abnormalities in the fetal heart rate tracing. Placental abruption occurs in 0.4% to 1.0% of all pregnancies. However, the pathophysiology remains incompletely understood. We present a review of the pathophysiology, diagnosis, and management of placental abruption, exploring overlapping processes which contribute to premature placental separation. Classic findings and limitations of ultrasound in evaluating placental abruption are explained. Finally, we discuss the management of placental abruption based on gestational age, fetal status, and maternal hemodynamic stability.

Precision medicine approaches to cancer treatment aim to exploit genomic alterations that are specific to individual patients to tailor therapeutic strategies. Yet, some targetable genes and pathways are essential for tumor cell viability even in the absence of direct genomic alterations. In underrepresented populations, the mutational landscape and determinants of response to existing therapies are poorly characterized because of limited inclusion in clinical trials and studies. One way to reveal tumor essential genes is with genetic screens. Most screens are conducted on cell lines that bear little resemblance to patient tumors, after years of culture under nonphysiologic conditions. To address this problem, we aimed to develop a CRISPR screening pipeline in three-dimensionally grown patient-derived tumor organoid (PDTO) models. A breast cancer PDTO biobank that focused on underrepresented populations, including West African patients, was established and used to conduct a negative-selection kinome-focused CRISPR screen to identify kinases essential for organoid growth and potential targets for combination therapy with EGFR or MEK inhibitors. The screen identified several previously unidentified kinase targets, and the combination of FGFR1 and EGFR inhibitors synergized to block organoid proliferation. Together, these data demonstrate the feasibility of CRISPR-based genetic screens in patient-derived tumor models, including PDTOs from underrepresented patients with cancer, and identify targets for cancer therapy. Significance: Generation of a breast cancer patient-derived tumor organoid biobank focused on underrepresented populations enabled kinome-focused CRISPR screening that identified essential kinases and potential targets for combination therapy with EGFR or MEK inhibitors. See related commentary by Trembath and Spanheimer, p. 407.

IMPORTANCE/UNASSIGNED:Chronic pain is common among individuals with dialysis-dependent kidney failure. OBJECTIVE/UNASSIGNED:To evaluate the effectiveness of pain coping skills training (PCST), a cognitive behavioral intervention, on pain interference. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This multicenter randomized clinical trial of PCST vs usual care was conducted across 16 academic centers and 103 outpatient dialysis facilities in the US. Adults undergoing maintenance hemodialysis and experiencing chronic pain were randomly assigned to PCST or usual care in a 1:1 ratio. Participants were followed in the trial for 36 weeks. Enrollment began on January 4, 2021, and follow-up ended on December 21, 2023. INTERVENTIONS/UNASSIGNED:PCST consisting of 12 weekly coach-led sessions via video or telephone conferencing, followed by 12 weeks of daily interactive voice response sessions. Usual care had no trial-driven pain intervention. MAIN OUTCOMES/UNASSIGNED:The primary outcome was pain interference measured with the Brief Pain Inventory (BPI) Interference subscale (score range of 0-10, with higher scores indicating more pain interference). Secondary outcomes included pain intensity, pain catastrophizing, quality of life, depression, and anxiety. RESULTS/UNASSIGNED:A total of 643 participants (mean [SD] age, 60.3 [12.6] years; 288 [44.8%] female) were randomized, with 319 assigned to PCST and 324 assigned to usual care. At week 12 (primary end point), the PCST group had a larger reduction in the BPI Interference score than the usual care group (between-group difference, -0.49; 95% CI, -0.85 to -0.12; P = .009). The effect persisted at week 24 (between-group difference in BPI Interference score, -0.48; 95% CI, -0.86 to -0.11) but was diminished at week 36 (between-group difference in BPI Interference score, -0.34; 95% CI, -0.72 to 0.04). A decrease in BPI Interference score greater than 1 point (minimal clinically important difference) occurred in 143 of 281 participants (50.9%) in the PCST group vs 108 of 295 participants (36.6%) in the usual care group at 12 weeks (odds ratio, 1.79; 95% CI, 1.28-2.49) and 142 of 258 participants (55.0%) in the PCST group vs 113 of 264 participants (42.8%) in the usual care group at 24 weeks (odds ratio, 1.59; 95% CI, 1.13-2.24). Favorable changes with PCST were also apparent for secondary outcomes of pain intensity, quality of life, depression, and anxiety at weeks 12 and/or 24, as well as for pain catastrophizing at weeks 24 and 36. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of patients undergoing maintenance hemodialysis, PCST had benefits on pain interference and other pain-associated outcomes. While the effect on the overall cohort was of modest magnitude, the intervention resulted in a clinically meaningful improvement in pain interference for a substantial proportion of participants. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04571619.

PURPOSE/OBJECTIVE:To better understand the occurrence of splenic disease as a potential manifestation of babesiosis by retrospectively estimating the frequency of acute splenic injury on abdominal and pelvic CT in a cohort of patients with active babesia infection. MATERIALS AND METHODS/METHODS:In a search of our single institution, suburban teaching community hospital database, 57 patients were found to have positive babesia infection between the years 2021-2023. 29 of these patients underwent abdominal and pelvic CT (22 with and 7 without intravenous contrast), and 3 underwent abdominal ultrasound without any CT. The imaging was reviewed for the presence or absence of splenic abnormalities, and for follow-up imaging. Parasitemia levels at the time of imaging were also reviewed; parasitemia levels < 4% are associated with mild to moderate disease, whereas parasitemia levels > 4% are associated with severe disease. RESULTS:21/32 (66%) patients who underwent any type of abdominal imaging (ultrasound, MRI, and CT) had splenomegaly. Of the 22 patients who had IV contrast-enhanced CT scans, 6 were found to have splenic infarction (27%). One of these 22 patients had multiple rounded non-peripheral hypoenhancing foci on both CT and MRI which did not meet criteria for infarction, in association with splenomegaly, and which resolved after treatment. 0/6 patients in the splenic infarction group had parasitemia levels greater than 4%, while 4 of the 16 patients (4/16) without infarction had parasitemia levels of greater than 4%. CONCLUSION/CONCLUSIONS:Our study showed that splenic disease in patients with babesiosis mostly took the form of splenomegaly, and in a substantial minority of patients as splenic infarction. There were no cases of splenic rupture and perisplenic hematoma in our case series, likely reflecting a limitation of the relatively small study size. Concordant with prior studies, we found no identifiable association between parasitemia levels and the presence of splenic infarction.

The organization of a cardio-oncology clinic and overall program is designed to provide comprehensive cardiovascular care to patients who are at risk of or have developed cardiovascular sequelae during or following cancer treatments. In this article, we summarize the core components of a contemporary cardio-oncology program, including its core members (cardiologists, oncologists, clinical pharmacists, advanced practice providers, nurses, and coordinators), key services (risk assessment, treatment planning, cardiac imaging, intervention, and management), and practical integration within the health care system.

The differential influence of sex on premature mortality in schizophrenia is unclear. This study assessed the differences in all-cause and specific cause mortality risks in people with schizophrenia compared to several control groups stratified by sex. We conducted a PRISMA 2020-compliant systematic review and random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) for people with schizophrenia, comparing by sex. We measured publication bias and conducted a quality assessment through the Newcastle-Ottawa scale. We meta-analyzed 43 studies reporting on 2,700,825 people with schizophrenia. Both males and females with schizophrenia had increased all-cause mortality vs. comparison groups (males, RR=2.62, 95%CI 2.35-2.92; females, RR=2.56, 95%CI 2.27-2.87), suicide (males, RR=9.02, 95%CI 5.96-13.67; females, RR=12.09, 95%CI 9.00-16.25), and natural cause mortality (males, RR=2.11, 95%CI 1.88-2.38; females, RR=2.14, 95%CI 1.93-2.38). No statistically significant differences in sex-dependent mortality risk emerged. There was an age-group-dependent increased mortality risk in females < 40 years vs. >/=40 years old (RR=4.23/2.17), and significantly higher risk of death due to neurological disorders (dementia) in males vs. females (RR=5.19/2.40). Increased mortality risks were often associated with specific modifiable risk factors. The increased mortality risk did not improve over time, calling for more studies to identify modifiable factors, and for better physical healthcare for males and females with schizophrenia.

OBJECTIVE:To compare hospitalization rates between African American (AA) and European American (EA) deceased-donor (DD) kidney transplant (KT) recipients during over a10-year period. METHOD/METHODS:Data from the Scientific Registry of Transplant Recipients and social determinants of health (SDoH), measured by the Social Deprivation Index, were used. Hospitalization rates were estimated for kidney recipients from AA and EA DDs who had one kidney transplanted into an AA and one into an EA, leading to four donor/recipient pairs (DRPs): AA/AA, AA/EA, EA/AA, and EA/EA. Poisson-Gamma models were fitted to assess post-transplant hospitalizations. RESULT/RESULTS:Unadjusted hospitalization rates (95% confidence interval) were higher among all DRP involving AA, 131.1 (122.5, 140.3), 134.8 (126.3, 143.8), and 102.4 (98.9, 106.0) for AA/AA, AA/EA, and EA/AA, respectively, compared to 97.1 (93.7, 100.6) per 1000 post-transplant person-years for EA/EA pairs. Multivariable analysis showed u-shaped relationships across SDoH levels within each DRP, but findings varied depending on recipients' race, i.e., AA recipients in areas with the worst SDoH had higher hospitalization rates. However, EA recipients in areas with the best SDoH had higher hospitalization rates than their counterparts. CONCLUSIONS:Relationship between healthcare utilization and SDoH depends on DRP, with higher hospitalization rates among AA recipients living in areas with the worst SDoH and among EA recipients in areas with the best SDoH profiles. SDoH plays an important role in driving disparities in hospitalizations after kidney transplantation.

BACKGROUND/UNASSIGNED:Caregiving has been associated with high blood pressure in middle-aged and older women, but this relationship is understudied among younger Black women, a population at high risk for hypertension. We examined the associations of caregiving stress and caregiving for high-needs dependents with incident hypertension among reproductive-age women in the JHS (Jackson Heart Study), a cohort of community-dwelling Black adults. METHODS/UNASSIGNED:We included 453 participants, aged 21 to 44 years, with blood pressure <140/90 mm Hg, and not taking antihypertensive medication at baseline (2000-2004). Caregiving stress over the past 12 months was assessed via a single item in the global perceived stress scale. Caregiving for a high-needs dependent status was assessed via a question on hours per week spent caregiving for children (≤5 years or disabled) or older adults. Incident hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or self-report of taking antihypertensive medication at follow-up exams in 2005 to 2008 and 2009 to 2013. RESULTS/UNASSIGNED:Over a median follow-up of 7.4 years, 43.5% of participants developed hypertension. Participants with moderate/high versus no/low caregiving stress had a higher incidence of hypertension (51.7% versus 40.6%). Higher caregiving stress was associated with incident hypertension after adjustment for sociodemographic and clinical factors, health behaviors, and depressive symptoms (hazard ratio, 1.39 [95% CI, 1.01-1.94]). Being a caregiver for a high-needs dependent was not associated with incident hypertension (adjusted hazard ratio, 0.88 [95% CI, 0.64-1.21]). CONCLUSIONS/UNASSIGNED:Higher caregiving stress among reproductive-age Black women was associated with incident hypertension. Hypertension prevention approaches for this high-risk population may include caregiving stress management strategies.