Publications by Year: 2025

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory disorder responsible for the global pandemic and widespread mortality. Circular RNAs (circRNAs), one of the newest forms of noncoding RNAs (ncRNAs), are important regulators of the host immune response and viral replication through sponging of microRNAs (miRNAs). This work aims to look at the expression and functions of hsa_circ_0009910/hsa-miR-145-5p/IFN beta 1 (IFNB1) in SARS-CoV-2-related infection and the molecular mechanisms that underpin them. In the experimental phase of the study, total RNA was isolated from the peripheral blood mononuclear cells (PBMCs) of 48 patients with symptomatic COVID-19, 48 patients with nonsymptomatic COVID-19, and 48 negative controls, and then cDNA was synthesized. Next, the expression of these genes was examined with quantitative real-time PCR (qRT-PCR). A receiver operating characteristic (ROC) curve was created to assess each gene's potential as a biomarker. The interactions of hsa_circ_0009910, hsa-miR-145-5p, and IFNB1, also the functional and pathway enrichment analyses, were detected by bioinformatics analysis. When compared with the negative control group, the expression of hsa_circ_0009910 in both symptomatic and nonsymptomatic groups, and IFNB1 in the symptomatic group was higher in the COVID-19 patients. Furthermore, the relative expression of hsa-miR-145-5p in the symptomatic and nonsymptomatic groups was lower than that in the negative control group. In addition, there was a positive correlation between hsa_circ_0009910 and IFNB1 expression, as well as a negative correlation between hsa-miR-145-5p, hsa_circ_0009910, and IFNB1 expressions. hsa-miR-145-5p has a higher area under the curve and may be a more effective biomarker to distinguish COVID-19 patients from the healthy controls, based on ROC curve study, but further study is needed. In conclusion, our data show that the hsa_circ_0009910/hsa-miR-145-5p/IFNB1 triple network may play a role in the pathogenesis of COVID-19 and can be considered a therapeutic target in COVID-19 patients.

Weight stigma in healthcare contributes to poor patient outcomes, emotional harm, and avoidance of care. Healthcare systems are often perceived as hostile environments for many larger-bodied people who often report feeling judged, dismissed or denied appropriate treatment. Despite growing awareness, most medical educational programs and healthcare systems do not address weight bias directly. Persuading clinicians and staff to disrupt the traditional medical paradigm and instead adopt a size-inclusive perspective requires educational materials that push the envelope without pushing learners off a cliff. This paper describes the development of a weight-inclusive e-course designed to raise awareness of the impact of anti-fat bias in medicine. Grounded in the philosophical frameworks of Health at Every Size™ (HAES™) and Trauma-Informed Care (TIC), the course was co-created by a multidisciplinary team including clinicians, educators, activists, and individuals with lived experience. The collaborative process emphasized shared leadership, inclusive design, and emotional safety. We detail the course's development over six months of weekly virtual meetings, including content creation, conflict resolution, accessibility planning, and evaluation design. The course includes three tracks tailored to clinicians, staff, and patients, and integrates practical tools for weight-neutral care. Lessons learned from this process offer a replicable model for inclusive curriculum design. Our aim is for learners to engage deeply with this work in order to fully reap the benefits for themselves and their patients. Institutions seeking to address weight stigma can use this framework to foster respectful, equitable care for people in all bodies.

BACKGROUND: Among diffuse midline gliomas with H3K27-altered with MAPK pathway mutations, those with BRAF V600E mutations show the most histologic variability and potential for targeted therapy, yet remain incompletely characterized. We present a series of such tumors, focusing on imaging, histologic, molecular, and therapeutic features.

METHODS: Pathology archives from 2016 to 2025 at our institution were searched for gliomas with H3K27M/BRAF V600E mutations. Clinical history, imaging, histology, molecular findings, therapy, and outcomes were reviewed.

RESULTS: Eight patients were identified (6 males, 2 females; age 3-18 years, average 11). Six tumors were thalamic, one cervical, and one suprasellar. Histology fell into three categories: low-grade glioma-like (n = 3), ganglioglioma-like (n = 3), and high-grade glioma-like (n = 2). Tumors with low-grade morphology had no additional clinically significant mutations, while high-grade tumors had co-occurring variants including TERT, 1q/5q gains, and polysomy 7. Two tumors had no methylation class match; two clustered with diffuse midline glioma, and one clustered with high-grade glioma with piloid features. Six patients had maximal safe resections, and two had biopsies (1 low-grade, 1 high-grade). All received BRAF/MEK inhibitors; six also had radiation, and two had chemotherapy. The two patients with high-grade tumors had outcomes similar to classic H3K27M diffuse midline gliomas (both deceased at 17 and 12 months). Patients with low-grade glioma or ganglioglioma-like tumors had better outcomes (all alive, average 38-month follow-up, range 6-80 months).

CONCLUSION: H3K27M/BRAF V600E-mutant gliomas may represent a distinct subgroup, with outcomes linked to histologic and co-occurring molecular features. Targeted therapy and a surgical approach may support long-term survival in low-grade cases.

BACKGROUND: HIV cure-related research often include analytical treatment interruptions (ATIs), which are monitored pauses in antiretroviral therapy (ART) to determine whether interventions can stimulate viral control without ART. While ATIs have been conducted in high-income countries, scale-up in low-income HIV high-burden countries in sub-Saharan Africa raise unique ethical, social, and practical challenges. HIV cure-related trials focus on participants without considering the experiences of partners and family members. Here, we explore the perspectives of partners and family members, including their emotional, relational, and mental health, during an ATI-inclusive HIV cure trial conducted in Durban, South Africa.

METHODS: We conducted a qualitative socio-behavioral study to explore the experiences of close contacts of ATI trial participants. Between November 2022 and June 2024, we interviewed partners and family members referred by trial participants. Interviews explored understanding of the trial, emotional and relational impacts, and concerns about ATIs. The interviews were conducted in English and/or isiZulu, transcribed, translated, and analyzed using content analysis to identify themes related to partner protections, trial communication, and psychosocial support.

RESULTS: Ten participants comprised five male partners (two living with HIV, three without) and five female family members (two mothers, two sisters, one cousin). Most had limited knowledge of HIV cure research but expressed hope for its advancements alongside concerns about ART discontinuation and viral rebound. Partners without HIV valued pre-exposure prophylaxis (PrEP) but reported inconsistent use, while partners with HIV feared re-infection during viral rebound. Mothers expressed concerns about ATIs, while sisters sought clearer information. Participants recommended improved communication, partner protections and psychosocial support, while acknowledging the trial's scientific importance.

CONCLUSION: ATI-inclusive HIV cure trials affect participants and their close social networks comprised of family members and intimate partners. Ethical trials are responsible for ensuring the safety of participants and other impacted groups. Family and partners were a critical source of support for trial participants, but have been underutilized in ATI-inclusive trials. Leveraging this existing support network in future ATI trials may improve safety while facilitating recruitment, willingness to discontinue ART during ATIs, prevent early ATI discontinuation, support adherence to frequent visits and sampling requirements, improving overall trial success.

PURPOSE: To compare the effect estimates obtained from patients with different levels of electronic health record (EHR)-continuity in four empirical studies: risk of pneumonia among 1) new users of proton pump inhibitors (PPI) vs H2 receptor antagonists, or 2) new users of PPI vs non-PPI users; risk of major bleeding among 3) new users of warfarin vs direct-acting oral anticoagulants, or 4) new users of oral anti-coagulants (OAC) vs non-OAC users.

PATIENTS AND METHODS: Patients were identified in 2 US EHR systems (MA system, NC system) linked with Medicare claims data (2007/1/1 - 2014/12/31) separately. We calculated incidence rates (IR), incidence rate differences (IRD), and hazard ratios (HR) in the total linked study population and after excluding patients with the lowest 25%, 50%, or 75% of EHR-continuity scores. We quantified bias in IRD and propensity score (PS) decile-adjusted HR.

RESULTS: In the MA system, IRs based on EHR-only data underestimated true rates by 44.1% to 76.2%, reduced to 12.9% to 46.5%. After excluding the lowest 75% of EHR-continuity patients, underestimation was more pronounced in non-user comparator designs. Absolute IRD bias was small for PPI vs H2RA (0.4%) and warfarin vs DOAC (0.7%), but larger for PPI vs non-PPI (19.1%) and OAC vs non-OAC (7.8%). Relative HR bias was 13.3% (PPI vs H2RA), 18.9% (PPI vs non-PPI), 3.0% (warfarin vs DOAC), and 31.5% (OAC vs non-OAC). Excluding lower-continuity patients and PS adjustment reduced IRD bias, while restricting to higher-continuity patients modestly improved HR bias.

CONCLUSION: Limiting analyses to patients with higher EHR-continuity can reduce IR underestimation and bias in effect estimates, particularly on the IRD scale. While PS adjustment mitigates some bias, EHR-discontinuity remains a source of bias, especially in studies using non-user comparators. These findings underscore the importance of balancing EHR-continuity with sample size considerations in pharmacoepidemiologic research.

BACKGROUND: Spontaneous intracranial hypotension syndrome (SIH)-induced chronic subdural hematoma (CSDH) often presents with orthostatic headaches but is frequently misdiagnosed, leading to inappropriate treatments like fatal hematoma drainage instead of epidural blood patches. In clinical practice, reliable and quantitative diagnostic criteria for this condition are lacking. This study uses initial CT scans to identify novel radiographic markers for accurately diagnosing SIH-induced CSDH.

METHODS: We retrospectively reviewed 310 consecutives hospitalized CSDH cases from January 2008 to May 2023. Among these, 54 were bilateral, with 11 induced by SIH; two secondary intracranial hypotension cases were excluded. We analyzed nine primary SIH-induced cases, comparing clinical and preoperative CT features with 43 non-SIH bilateral cases, focusing on the parasagittal subdural space (PSS) volume. We also conducted propensity score matching to validate our findings.

RESULTS: Patients with SIH-induced bilateral CSDH were significantly younger than those without SIH (mean age 54.7 vs. 76.2 years; P < 0.001). Orthostatic headache was more common in the SIH group (66.7% vs. 2.3%, P < 0.001). While hematoma volumes were similar, PSS volume was significantly larger in the SIH group (mean 15.0 vs. 5.1 mL, P = 0.007). ROC analysis identified an exploratory PSS cut-off of 11.1 mm², which yielded a sensitivity of 86% and a specificity of 66.7% (P = 0.009). Linear regression and qualitative assessments indicated a significant association between PSS volume and crural-and-ambient cistern obliteration, as well as cerebellar ptosis in the SIH group (P < 0.001).

CONCLUSION: A preserved PSS on coronal CT represents a novel, quantitative marker for SIH-induced CSDH and may serve as a practical diagnostic clue, particularly when MRI is unavailable.

OBJECTIVE: To evaluate bleeding rates among patients who received a mechanical aortic valve replacement (mAVR) treated with warfarin monotherapy versus warfarin with a therapeutic parenteral anticoagulant bridge.

METHODS: This retrospective, single-center, observational study included patients at least 18 years old who received an mAVR and had anticoagulation ordered by the end of postoperative day 2. Exclusion criteria included an INR goal other than 2-3, a hypercoagulable state, postoperative mechanical circulatory support, delayed sternal closure, pregnancy or incarceration. The primary outcome was International Society of Thrombosis and Hemostasis major bleeding until hospital discharge or 30 days after valve replacement, whichever came first. Secondary outcomes included thromboembolic events, hospital length of stay, and mortality.

RESULTS: A total of 143 patients were included in the final analysis, 112 patients in the therapeutic anticoagulation bridge group and 31 patients in the warfarin monotherapy (no-bridge) group. Eighty-seven percent of the patients were white and 69.2% were male, and the median age was 49 years (interquartile range [IQR], 41-58 years). Sixteen patients (14.3%) in the bridge group experienced a major bleed, compared to 0 patients in the no-bridge group (P = .02). Thromboembolic events occurred in 6.5% of patients in the no-bridge group versus 2.7% in the bridge group (P = .30). There was no difference in mortality between the 2 groups (P = .99).

CONCLUSIONS: The use of therapeutic parenteral anticoagulation with warfarin after mAVR significantly increased the rate of major bleeding compared to warfarin monotherapy. Larger prospective studies are needed to confirm these findings.

BACKGROUND: Pain is common among patients with advanced cancer and is often inadequately controlled. Opioids are central to treatment; yet, self-management is challenging, and clinicians lack scalable tools to monitor and support patients between visits.

OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of MyPainPal (Dana-Faber Cancer Institute), a novel mobile health app designed to optimize cancer pain management. MyPainPal combines daily surveys assessing symptoms and analgesic use, algorithmic self-management support, tailored psychoeducation, and clinician monitoring. Secondary objectives were to explore preliminary clinical impact and identify priorities for refinement.

METHODS: This single-arm pilot study enrolled adults with advanced malignancies using opioids for moderate-to-severe pain from an outpatient palliative care clinic at a comprehensive cancer center. Participants used MyPainPal for 28 days while nurses monitored symptom responses via a secure portal, and also completed structured surveys at end-of-study. Primary assessment of usability and acceptability included the System Usability Scale (SUS; range 0-100), the Acceptability E-Scale (range 6-30), and ratings of satisfaction using a 5-point Likert scale. Semistructured debriefing interviews explored user experience, perceived impact, and suggestions for optimization.

RESULTS: Twenty participants with advanced cancer enrolled, with a mean age of 57 (SD 12.3) years, 55% (11/20) female, 80% (16/20) non-Hispanic White, with mixed cancer types. Over the 28-day study, patients logged into MyPainPal a median of 14 (IQR 8-17) times, and completed a median of 8 (IQR 5-14) symptom surveys, reflecting mean of 36% (SD 20%) of eligible (out-of-hospital) days on study. Usability and acceptability ratings of MyPainPal were high (mean SUS 78.3, SD 16.2; mean Acceptability E-Scale 24.0, SD 4.4); 79% rated overall satisfaction of greater than or equal to 4/5. Twenty percent of surveys generated an alert, prompting nurse outreach. In response, 5 participants had symptom medications changed and 2 had medication errors corrected. In debriefing interviews, many participants described that the intervention reduced barriers to pain reporting and facilitated timely and constructive interactions with care teams for symptom management. Several noted that the intervention validated their pain experience, reduced stigma around opioid use, enabled constructive conversations with providers, and promoted self-management. Patients recommended several survey modifications, including reducing their frequency and enabling more nuanced pain assessments. Participants underused the educational resources and suggested that they be featured more prominently. Some patients suggested that the MyPainPal app should be introduced earlier in patients' cancer pain trajectory when pain needs are higher and opioid management is novel.

CONCLUSIONS: In this pilot study, MyPainPal demonstrated feasibility, acceptability, and preliminary evidence of potential clinical impact among patients with advanced cancer receiving palliative care. The app has been rebuilt and optimized with attention to patient feedback and in preparation for a future efficacy study.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03717402; https://clinicaltrials.gov/study/NCT03717402.

PURPOSE: To investigate area under diaphragm (AUD) obtained by dynamic digital radiography (DDR) for the differentiation between normal subjects and chronic obstructive pulmonary disease (COPD) patients.

METHODS: This retrospective study included healthy volunteers and COPD patients recruited from 2009 to 2014 at Fukujuji Hospital, who received DDR and pulmonary functional test. AUD was defined as an area under a hemidiaphragm and above the line connecting the ipsilateral costophrenic angle to the top of the hemidiaphragm on DDR image. AUD in full inspiration minus AUD in full expiration (ΔAUD) was also calculated. The diaphragmatic surface was demarcated manually on DDR image to calculate AUD. Three-group comparison of AUD and ΔAUD among normal, mild COPD, and severe COPD subjects was tested with one-way analysis of variance, followed by multiple comparison with Tukey-Kramer method. The diagnostic accuracy of COPD by ΔAUD was assessed using receiver-operating-characteristics (ROC) curve.

RESULTS: Sixty-eight participants (36 men, 29 COPD patients) were enrolled. AUD in full inspiration was larger in healthy volunteers than in COPD patients (right, p < 0.001; left, p = 0.02). ΔAUD were different in the three-group comparison (right, normal, 208.7 ± 184.6 mm2, mild COPD, -18.1 ± 117.5 mm2, severe COPD -97.5 ± 150.0 mm2, p < 0.001; left, normal, 254.9 ± 131.5 mm2, mild COPD, -12.5 ± 136.5 mm2, severe COPD, -100.7 ± 134.1 mm2, p < 0.001). ROC curve showed high diagnostic performance of COPD by unilateral ΔAUD (right, area-under curve 0.942; left, area-under-curve 0.965).

CONCLUSION: The value of ΔAUD was smaller according to the severity of COPD. ΔAUD can be helpful in distinguishing healthy subjects from COPD patients.