Citations

Background: Housing instability and HIV are both associated with early onset of aging-related health conditions, including frailty. However, little is known about the relationship between housing and frailty among people with HIV. Methods: We analyzed data on adults in HIV care collected during routine clinical visits at 6 sites within the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) between 2019 and 2024. We measured frailty using a previously validated approach, defined as having at least three of four components (fatigue, weight loss, immobility, inactivity) vs. less than three components. Housing status was based on self-perceived living situation in the past month (“Stable,” “Unstable,” “Homeless,” or “Don’t know”). We estimated the association between most recent housing status and frailty with prevalence ratios from relative risk regression adjusted for sociobehavioral and clinical characteristics. Results: Among 6961 people with HIV (84% men, 16% women) with a median age of 52 years (IQR: 40–60), 11% ( n = 760) were frail and 9% ( n = 625) were unstably housed (5% unstable, 3% homeless, 1% do not know). Compared to individuals with stable housing, the prevalence of frailty more than doubled among those experiencing unstable housing [prevalence ratio = 2.41, 95% confidence interval (95% CI): 1.95–2.97] or homelessness (prevalence ratio = 2.05, 95% CI: 1.56–2.69). Stratified analyses indicated stronger associations among younger vs. older individuals and among those virally suppressed vs. unsuppressed. Conclusion: Housing instability and frailty were both prevalent and strongly associated among adults in HIV care, including within younger and virally suppressed subgroups. These findings highlight the importance of social determinants of health for clinical outcomes among all people with HIV.

Purpose of review Sulfate is essential for the sulfation of proteoglycans to maintain cell function. The mechanisms regulating the ‘ins and outs’ of systemic sulfate balance remain incompletely understood. SLC26A1 is an anion exchanger expressed in the kidney. It has recently been identified as a key regulator of plasma sulfate homeostasis in humans. This review summarizes current insights into SLC26A1 function and its role in human diseases. Recent findings Slc26a1-knockout mouse models exhibit reduced plasma sulfate and abnormal sulfate and oxalate homeostasis, accompanied by augmented susceptibility to acetaminophen-induced liver injury and kidney stone disease, although findings on oxalate homeostasis are inconsistent. In humans, rare and common SLC26A1 variants are associated with hyposulfatemia, musculoskeletal abnormalities, and, in some cases, nephrolithiasis. Functional assays confirm disrupted sulfate and oxalate transport of damaging variants. However, the knockout mouse models have been incompletely characterized, and few patients with damaging SLC26A1 variants have been characterized regarding sulfate and oxalate homeostasis and associated diseases. Summary SLC26A1 emerges as a key regulator of sulfate homeostasis, with potential roles in hepatic detoxification, skeletal integrity, and kidney stone disease. Additional mouse models with tissue-specific gene deletion are needed to delineate the role of SLC26A1 in sulfate and oxalate homeostasis as well as disease pathogenesis. Identification of additional patients with damaging variants in SLC26A1 as well as larger population studies may help to elucidate causal relationships of SLC26A1 activity with clinical outcomes.

Background: Increasing maternal body mass index (BMI) represents a risk factor for Gestational Diabetes Mellitus (GDM) and adverse obstetrical and perinatal outcomes. Objective: To stratify clinical outcomes for pregnancies affected by GDM according to maternal BMI. Methods: Retrospective cohort study including individuals ≥18 years of age who were diagnosed with GDM from 2018 to 2022. Universal GDM screening was employed with a 50 g oral glucose challenge test ± a 100 g oral glucose tolerance test. Maternal demographics, preexisting medical conditions, and selected obstetric and neonatal morbidities were evaluated. Results: A total of 2193 pregnancies in 2110 women affected by GDM were identified. This included 506 (23.0%) with normal baseline maternal BMI, 596 (27.2%) with overweight, and 1091 (49.7%) with obese BMI. Adverse maternal outcomes were more frequent in the obese compared to overweight or normal BMI categories (cesarean delivery: normal 26.9% vs. overweight 28.5% vs. obese 40.9%; p < 0.001; hypertensive disorders of pregnancy: normal 8.7% vs. overweight 12.1% vs. obese 16.8%; p < 0.001). Postpartum glucose intolerance was higher in women with obesity (normal 7.3% vs. overweight 5.9% vs. obese 14.9%; p < 0.001). Infants born to mothers with obesity had higher birthweights (normal 3.3 kg vs. overweight 3.4 kg vs. obese 3.5 kg; p < 0.001), were more likely to have neonatal hypoglycemia (normal 29.4% vs. overweight 24.3% vs. obese 41.9%; p < 0.001) and require intensive care unit admission (normal 8.1% vs. overweight 5.9% vs. obese 11.9%; p < 0.001). Conclusions: Patients with GDM and baseline BMI in the obese range experienced the highest rate of adverse outcomes, while those with overweight BMI had similar outcomes to individuals who had normal BMI at baseline.

592 Background: While not all fevers occurring during hematopoietic stem cell transplantation (HCT) are dangerous, episodes of febrile neutropenia tend to be managed aggressively given the significant mortality and morbidity associated with infectious complications of transplantation. This can potentially lead to unnecessary diagnostic testing, antibiotic treatment, and prolonged hospital stays for non-infectious fever etiologies such as engraftment. Our group has previously demonstrated that high-frequency body temperature monitoring (HFTM) using a wearable device detects fevers earlier in transplant recipients (Flora et al, Cancer Cell, 2021). We hypothesized that applying supervised machine learning to HFTM data collected from inpatient allogeneic HCT patients would allow for accurately distinguishing between non-infectious and infectious etiologies of fever and could potentially guide safe de-escalation of antibiotics. Methods: We analyzed 74 independent fever events detected in HCT patients (n=42) outfitted with an FDA-cleared, wireless sensor measuring axillary temperatures every 2 minutes for the duration of their respective hospitalizations. After data filtering, independent fever events were then retrospectively grouped by fever etiology using physician-determined annotation as previously described (Flora et al., 2021). A split ratio of 80:20 was used to create training and test sets from the parent data set, consisting of 59 and 15 fever events for each split, respectively. Training sets were used to create a classification algorithm identifying bacterial infections requiring antibiotics using the machine learning model XGBoost. The performance of this model was then evaluated using test sets of the remaining fevers (n=15). Results: Averaging over 1000 test sets of 15 independent fevers comprising 5 bacterial infection-related fevers and 10 non-infectious fevers, our model correctly identified 82% (mean recall) of cases requiring antibiotics with a mean precision of 0.41. The model also correctly identified 42% of non-infectious fevers (mean true negative rate, 0.42) that would otherwise have been treated with unnecessary antibiotics. The mean AUCPR was 0.58, with the best performing individual model achieving an AUCPR of 0.97. Conclusions: The preliminary results of this study demonstrate that our classification model shows promise for differentiating fevers requiring antibiotics due to bacterial infections from other non-infectious fever etiologies. Prospective studies further developing supervised machine learning models for subcategorization of febrile neutropenia could pave the way for safely de-escalating antibiotics in HCT and other immunocompromised patients undergoing cancer treatment monitored using HFTM.

469 Background: Febrile neutropenia (FN) is a potentially life-threatening complication of myelosuppressive chemotherapy. Multiple professional organizations, including the American Society of Clinical Oncology (ASCO), Infectious Diseases Society of America (IDSA), National Institute for Health and Care Excellence (NICE), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN), have developed clinical guidelines addressing FN management. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework offers a structured method for assessing the evidence underlying these recommendations. Methods: A comparative analysis was conducted across guidelines. Key domains, including definitions, risk stratification, empiric antimicrobial therapy, duration of antimicrobial therapy, use of granulocyte colony-stimulating factor (G-CSF), and antimicrobial prophylaxis were assessed. Recommendations were analyzed for concordance and the certainty of supporting evidence was appraised using the GRADE framework. The certainty of the evidence was graded as high, moderate, low, or very low. Results: All five guidelines uniformly defined FN as fever ≥38.3°C or sustained ≥38.0°C accompanied by neutropenia (absolute neutrophil count <500 cells/µL), despite very low-certainty evidence supporting these specific thresholds. Risk stratification using validated tools, such as the Multinational Association for Supportive Care in Cancer (MASCC) score and the Clinical Index of Stable Febrile Neutropenia (CISNE), is recommended based on moderate-certainty evidence. Empiric monotherapy with anti-pseudomonal beta-lactam agents is recommended across guidelines and supported by high-certainty evidence. Antifungal therapy is recommended for persistent fever beyond 4–7 days in high-risk patients based on low-certainty data. Variability was noted in the suggested duration of antibacterial therapy and the role of therapeutic G-CSF based on low-certainty evidence. Recommendations for antimicrobial prophylaxis are consistent across high-risk populations. Conclusions: Despite broad agreement in foundational management principles for febrile neutropenia, differences exist in the application of therapeutic G-CSF and the duration of empiric antibiotics. These findings underscore the need for high-quality clinical trials to inform harmonized, evidence-based recommendations. This synthesis identifies priority areas for stewardship initiatives and quality-of-care improvement.

345 Background: Pediatric febrile neutropenia (PFN) requires emergent evaluation due to risk of invasive bacterial infection. In the management of PFN, there are varying, accepted definitions for fever requiring emergency evaluation and neutropenia requiring admission. Problem statement: From September 1, 2022 - May 31, 2023, 15.1% (n = 11/73) of emergency department (ED) visits and 17.1% (n = 6/35) of admissions for PFN at Mayo Clinic Rochester may be considered unnecessary due to patients not meeting updated clinical criteria. Aim: Decrease unnecessary ED visits and hospitalizations for PFN by 50% from 15.1% to 7.5% (for ED visits) and from 17.1% to 8.6% (for hospitalizations) by 02/29/2024 without adversely impacting mortality from invasive bacterial infection. Methods: We used the DMAIC framework for process improvement. Interventions included (1) adoption of a higher fever definition for PFN, (2) adoption of a risk-stratified neutropenia definition for hospital admission, (3) provided electronic fever plans with definitions to all families, (4) re-iterated that parents call on-call provider with any concern for fever, (5) educated pediatric oncology staff on definition and management of fevers in pediatric oncology patients, and (6) educated pediatric emergency department staff on definition and management of fevers in pediatric oncology patients. Interventions were tested with rapid tests of change. Relevant clinical characteristics, variables, and outcomes for all patients from pediatric oncology were tracked for all encounters of pediatric oncology patients presenting to the ED for acute illnesses. Results: At baseline,15.1% (n = 11/73) of ED visits for PFN were considered unnecessary due to patients not meeting clinical criteria for emergency evaluation. Post-interventions, unnecessary ED visits for PFN had decreased to 3.4% (n = 1/32). At baseline, 17.1% (n = 6/35) of hospitalizations were considered unnecessary due to patients not meeting clinical criteria for admission. Post-interventions, 7.7% (n = 2/26) of hospitalizations were considered unnecessary. There were no patient deaths from invasive bacterial infection among this cohort at baseline or after interventions. Conclusions: Multiple interventions including adoption of a higher, accepted fever threshold and risk stratified neutropenia definition for PFN was associated with a reduction of unnecessary ED visits and hospitalizations for PFN without an increase in mortality from invasive bacterial infection. The projected medical expense savings of approximately $144,000-$210,000 per year.

230 Background: The burden of symptoms and financial toxicity are well-documented adverse effects of cancer treatments. Recently, logistic toxicity has emerged, referring to the detrimental impact of logistical demands associated with cancer treatment on patient well-being. For non- English speaking patients, language barriers can affect their treatment experience, increasing logistic burdens. Methods: Between September 2024 and May 2025, semi-structured qualitative interviews were conducted with 21 low English proficiency (LEP)/non-English speaking adults with cancer. The interviews explored logistic challenges faced due to LEP and its impact on patients' cancer care experience. Transcripts were analyzed using an inductive thematic analysis approach. Results: Of the 39 identified eligible individuals, 26 provided consent, and 21 (81%) completed the interview. The most common primary language of the participants was Spanish (9, 43%), followed by Somali (3, 14%), Arabic and Korean (2, 9%), and Amharic, Mandarin, Hmong, Russian, and Vietnamese (1, 5%). Seven major themes emerged regarding the logistic burdens of cancer care: (1) communication challenges, (2) navigating healthcare systems, (3) emotional distress from diagnosis and communication barriers, (4) financial toxicity, (5) transportation challenges, (6) adverse treatment effects, and (7) concerns about the political climate and its impact on resources. Conclusions: The increase in non-English languages in the U.S. highlights the need to understand the unique challenges faced by these patients. This study identified logistic toxicity themes consistent with previous research, while also revealing unique challenges. Further research is necessary to explore strategies to mitigate logistic burdens among those with LEP. Theme Illustrative Quotes Communication challenges “Communication with the psychologist was challenging … I couldn’t express myself effectively and it left me unsatisfied with the interaction.” Navigating healthcare systems “dealing with the insurance, it has been difficult … I have to depend on another person to help me” Emotional distress from diagnosis and communication barriers “In addition to my sickness, the lack of communication and understanding… makes me very sad.” Financial toxicity “...there's no income. There is nothing to feed our children.” Transportation challenges “I have to leave home 2 or 3 hours in advance because people will help me, not within my time, but within their own time.” Adverse treatment effects “I noticed weird feelings in my limbs. I'm not able to write down or hold anything. It makes everything difficult.” Concerns about current political climate and its impact on existing resources “… that they don't want Spanish spoken in the United States. They're not going to provide help for people like me at the hospitals…”

572 Background: Neoadjuvant endocrine therapy (NET) is sometimes used to shrink hormone receptor-positive (HR+) breast cancers to improve breast conservation rates and reduce axillary nodal burden. At the beginning of the COVID-19 pandemic, several organizations endorsed NET use to mitigate the harm of surgery delay when cancer operations were less available due to infection transmission concerns. However, the real-world patterns of NET during this period are understudied. This study investigated the alteration of NET utilization patterns during the COVID-19 pandemic in the United States using the National Cancer Database (NCDB). Methods: We identified patients diagnosed with stage I-III invasive HR+/human epidermal growth factor receptor 2-negative (HER2-) breast cancer between 2018-2022 in the NCDB. Estrogen receptor and/or progesterone receptor positivity was required for inclusion in the cohort. Receipt of NET was defined as initiation of endocrine therapy ≥ 14 days before the patient’s first surgical procedure. The study cohort generation and statistical analysis were conducted using Stata and R 4.4.3. A two-tailed p value < 0.05 was considered statistically significant. Results: 495,098 patients were included in the cohort, 195,371 in 2018-2019 (pre-pandemic), 91,686 in 2020 (early pandemic), 106,157 in 2021 (mid-pandemic), and 101,884 in 2022 (late pandemic). NET utilization was increased in the early pandemic compared to the pre-pandemic (seen in 5.8% vs 2.4% of the cohort, Chi-square p value < 0.001), but this use fell back to 3.4% in the mid-pandemic and 3.5% in the late-pandemic. The median (IQR) duration of NET was 15.7 (6.4-26.6) weeks in the pre-pandemic, 9.3 (5.4-18.7) weeks in the early pandemic, 13.2 (5.8-25.7) weeks in the mid-pandemic, and 12.0 (6-24.6) weeks in late pandemic (Kruskal-Wallis p value = 0.001). The transient increase in NET utilization during the early pandemic was more pronounced among patients with tumors < 5 cm and node-negative disease. Conclusions: Our study identified a significant shift in the utilization of NET for HR+/HER2- breast cancer during the COVID-19 pandemic. Pandemic-era NET policies produced a short-lived practice change that was only partially sustained once surgical access normalized. NET utilization (%) by subgroup and year for stage I-III HR+/HER2- breast cancer. Variable Category 2018-2019 2020 2021 2022 Overall NET Use 2.4 5.8 3.4 3.5 Age Group (years old) <50 2.2 4.9 3.9 4.0 >=50 2.4 6.0 3.3 3.4 Tumor Size <5 cm 2.0 5.5 2.9 3.1 >=5 cm 9.0 9.7 11.2 11.6 Histology Subtype Ductal 2.2 5.5 3.3 3.4 Lobular 3.6 7.1 4.4 4.8 Ductal/Lobular 2.6 6.2 4.3 3.6 Other 1.9 6.7 2.5 2.6 KI67 <20% 2.5 6.4 3.4 3.3 >=20% 2.3 5.5 3.5 3.7 Tumor Grade Well differentiated 1.9 5.8 2.4 2.6 Moderately differentiated 2.7 6.1 3.9 3.9 Poorly differentiated/undifferentiated 2.9 4.8 4.3 4.8 Node Positivity Positive 5.2 5.6 9.3 9.5 Negative 2.0 5.8 2.6 2.7

566 Background: Video telemedicine visits (VTVs) have the potential to overcome disparities in access to cancer care for many socially, geographically, and economically disadvantaged populations. Internet connectivity, digital literacy, and socioeconomic factors are traditionally cited as influencing VTV utilization. However, digital diffusion has occurred rapidly across several sectors, including healthcare, since the onset of the COVID-19 pandemic, and less is known about how these factors have evolved to influence VTV utilization behavior over this time. Through a qualitative approach, we aimed to: (1) explore the lived experiences of cancer patients who transitioned to VTV use as compared to those who persistently did not, and (2) identify similarities and differences between these two groups that could inform targeted interventions to support access and patient acceptance of VTVs in the setting of cancer care. Methods: During June 2024, we conducted semi-structured interviews with 24 patients (Mean age 71.3 years, range 42-88; female 50%) receiving ongoing, longitudinal cancer care at our academic medical center since July 2021 who had not used VTVs through at least October 2022. Using purposeful sampling, patients were equally divided according to VTV utilization behaviors defined as “transitioned users” (TU; i.e. those who transitioned to VTV utilization after October 2022) and “persistent non-users” (PNU). Transcripts were analyzed using a combined deductive–inductive thematic approach and categorized into themes of barriers and facilitators across three domains consistent with the COM-B model: capabilities (C), opportunities (O), and motivations (M). Results: TU patients frequently cited a reduction in travel and logistical considerations as a primary reason for uptake of VTVs. PNU patients frequently reported digital literacy barriers, particularly among older patients, as primary reasons for lack of VTV utilization. TU patients reported more experience and comfort in technical skills as compared to PNU participants. PNU patients also reported less frequent offering of VTV as an option by their care teams over time, implying they may have transitioned to VTV utilization if it had been offered with more regularity. Both study groups desired improved internet access and technical support to enhance (or, in the case of PNU patients, enable) VTV utilization. Conclusions: These findings suggest that multi-modal care delivery may best serve current patient populations, not requiring, yet offering VTV services as an adjunct to in-person care. Longer term, individual barriers to VTV use will also need to be addressed to further optimize access for patients who desire to incorporate this care modality.