Faculty Bibliography

BACKGROUND:Cognitive impairment is linked with increased risk of falls in people with multiple sclerosis (pwMS), but it is not clear whether cognitive performance may help to account for the discordance between fall-risk due to actual physiological functioning and the individual's perception of their fall-risk. This study examined the relationship between cognitive performance and the concordance/discordance of physiological and perceived fall-risk in pwMS. METHODS:) fall-risk. Cognitive performance was evaluated using the NeuroTrax computerized cognitive battery, which generates a global cognitive score (GCS) as well as scores for individual cognitive domains. RESULTS:group. CONCLUSION/CONCLUSIONS:In this study, one in 4 pwMS had a discordance between their physiological and perceived fall-risk. This discordance was not explained by cognitive performance.

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients with transplant-ineligible or transplant-deferred NDMM were randomly assigned to eight cycles of D-VRd or VRd followed by D-Rd or Rd until progression. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10^-

Bowel endometriosis is a complex condition predominantly impacting women in their reproductive years, which may lead to chronic pain, gastrointestinal symptoms, and infertility. This review highlights current approaches to the diagnosis and management of bowel endometriosis, emphasizing a multidisciplinary strategy. Diagnostic methods include detailed patient history, physical examination, and imaging techniques like transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI), which aid in preoperative planning. Management options range from hormonal therapies for symptom relief to minimally invasive surgical techniques. Surgical interventions, categorized as shaving excision, disc excision, or segmental resection, depend on factors such as lesion size, location, and depth. Shaving excision is preferred for its minimal invasiveness and lower complication rates, while segmental resection is reserved for severe cases. This review also explores nerve-sparing strategies to reduce surgical morbidity, particularly for deep infiltrative cases close to the rectal bulb, anal verge, and rectosigmoid colon. A structured, evidence-based approach is recommended, prioritizing conservative surgery to avoid complications and preserve fertility as much as possible. Comprehensive management of bowel endometriosis requires expertise from both gynecologic and gastrointestinal specialists, aiming to improve patient outcomes while minimizing long-term morbidity.

While there is agreement on the indications for intracranial pressure monitoring (ICPm) in patients with sTBI, there continues to be controversy concerning the ideal timing of its implementation. It is within this context that we decided to investigate whether a protocolization approach could optimize the timeliness of ICPm implementation. Neurosurgical and SICU providers agreed to a 3-tier protocol to identify patients with sTBI who could benefit from timelier ICPm implementation. The monthly compliance was monitored for a 9-month period. The study included a pre-protocolization group of 11 patients (2022) and a post-protocolization group of 9 patients (2023-2024). There was a trend toward earlier use of ICPm but the difference did not achieve statistical significance; there was no difference in the mortality rates between groups. A protocolization approach to the treatment of patients with sTBI developed with a consensus strategy may lead to earlier implementation of ICPm and possibly improved functional outcome.

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.

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.

The recent escalation of racism in the U.S. during the COVID-19 pandemic points to the importance of examining the association between experienced racism and sexual health. Based on data from a nationally representative survey conducted in the U.S. in October 2020 (n = 1,915), Chi-square tests and multivariable logistic regressions were estimated to examine the association between experience of racism and changes in sex life during the pandemic. We further performed a causal mediation analysis using the bootstrap technique to assess the mediating role of psychological distress in the observed association between the experience of racism and changes in sex life. Among the respondents, the proportions reporting better, worse, or no change in sex life were, respectively, 15%, 21%, and 64%. Experiencing racial discrimination during COVID-19 was significantly associated with worsening sex life (adjusted odd ratio [AOR] = 1.53; 95% confidence interval [CI] = 1.04, 2.25). Respondents with experienced racism were also more likely to report psychological distress (AOR = 1.68; 95% CI = 1.09, 2.59). About one-third (32.66%) of the observed association between experienced racism and worsening sex life was mediated through psychological distress. Addressing racism and its association with psychological distress has the potential to improve sexual health and reduce related racial and ethnic disparities.

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.

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.