Rhode Island Hospital

Tandem lesions (TLs) are a subtype of acute ischemic stroke, which involve an extracranial carotid lesion (ie, severe carotid stenosis ≥70%) with large vessel occlusion. While large vessel occlusion has a standard approach with mechanical thrombectomy (MT), the best practice for intervention of the carotid lesion is not well-established. Utilizing data from the ASSIST registry, we investigated the differences in clinical and procedural outcomes between acute versus nonacute stenting. The ASSIST registry (an international acute ischemic stroke MT prospective study) was utilized to identify the subgroup of patients with acute ischemic stroke secondary to TL who received MT. The TLs were grouped by MT+acute carotid stenting (CAS) versus MT+acute carotid nonstenting. The demographics and clinical outcomes (90-day modified Rankin Scale score) were compared between TL and non-TL groups, and between MT+CAS and MT+acute carotid nonstenting. Multivariable analyses were performed to determine independent predictors of clinical outcomes. A total of 183 of 1270 (14.4%) TLs were identified in the ASSIST registry. MT+CAS was performed in 83 of 183 (45.4%) subjects, and 100 of 183 (54.6%) received MT+acute carotid nonstenting. There are no significant differences at baseline between the 2 groups in the National Institutes of Health Stroke Scale score, Alberta Stroke Program Early Computed Tomography Score, or target vessel. Achieving a modified Rankin Scale score of 0 to 2 at 90 days was 70.9% in the MT+CAS group versus 48.9% in the MT+acute carotid nonstenting group (P=0.001), with a modified Rankin Scale score of 0 to 2 being significantly associated with the MT+CAS group in multivariable analysis (odds ratio, 2.14 [95% CI, 1.01-4.51]). There was no significant difference in mortality or symptomatic intracerebral hemorrhage between the groups. In acute ischemic stroke, secondary to TLs treatment with thrombectomy and acute carotid stenting is associated with improved 90-day functional outcome without an increase in symptomatic intracerebral hemorrhage compared with no acute stenting approach. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03845491.

NaV (voltage-gated sodium) channels drive cardiac excitability. Although NaV1.5 is the primary cardiac isoform, the composition and functional contributions of non-NaV1.5 isoforms in the heart remain unclear. Here, we developed a chemical-genetic mouse model (NaV1.5GX/GX) in which NaV1.5 can be selectively and reversibly inhibited by acyl- and aryl-sulfonamide compounds (GX [acyl- and aryl-sulfonamide compounds typically denoted by the name GX-### and associated items] drugs). Cardiac activity was assessed by electrocardiograms in vivo, and optical mapping was used for imaging of ex vivo hearts. Whole-cell voltage-clamp in tandem with validated toxins and isoform-selective inhibitors were used to examine sodium current composition. NaV1.5GX/GX mice exhibited normal cardiac function at baseline, but acute GX drug administration caused profound conduction defects and arrhythmias. Whole-heart optical mapping revealed dose-dependent chamber-specific sensitivity to NaV1.5 inhibition, with the right ventricle being the most sensitive, followed by the left ventricle, left atrium, and right atrium. Patch-clamp recordings of isolated cardiomyocytes with application of NaV isoform-selective inhibitors showed that NaV1.5 contributed 93% of sodium current in the left ventricle, 79% in the right ventricle, and 78% in the atria. Non-NaV1.5 isoforms were differentially enriched across chambers: NaV1.8 in the left ventricle, NaV1.1/1.3 in the right ventricle, and NaV1.2/1.6/1.7 in the atria. These results reveal a surprising chamber-specific isoform landscape of cardiac sodium currents, which may underlie the right ventricular predominant phenotype of Brugada syndrome. These data highlight non-NaV1.5 isoforms as potential mediators of chamber-specific cardiac pathologies and as pharmacological targets.

Staphylococcus aureusis a critical global health threat due to its multidrug resistance (MDR) and virulence. We examined the relationship between MDR and virulence in 250 clinical S. aureus isolates using the Galleria mellonella infection model. Alpha-hemolysin was the most prevalent toxin, with its gene, hla, present in the majority of hemolytic strains. Other virulence genes, including sigB, codY, fnbA, fnbB, clfA, saeS, sarA, arlS, yycG, spoVG, rot, and PVL, were widely distributed across methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) isolates. The ica gene showed a notable increase in expression in hospital-acquired (HA-MRSA) and community-acquired (CA-MRSA) strains. In vivo infections revealed that HA-MRSA strains were more virulent than vancomycin intermediate S. aureus VISA, CA-MRSA, MSSA, and an agr mutant strain, while locally sourced CA-MRSA exhibited the highest virulence among tested strains. Despite differences in antibiotic resistance, MRSA and MSSA shared largely similar virulence gene profiles. These findings highlight the complex interplay between MDR and virulence in S. aureus and emphasize the need for further mechanistic studies.Importance: S. aureus remains a major clinical concern due to its increasing multidrug resistance (MDR) and virulence. Understanding the relationship between resistance mechanisms and virulence is essential for guiding effective treatment and infection control. This study assessed the virulence potential of 250 MDR S. aureus isolates using a clinically relevant invertebrate model (G. mellonella), revealing key virulence gene profiles. Notably, CA-MRSA strains exhibited hypervirulence, with alpha-hemolysin as the most prevalent toxin and significant upregulation of the ica gene in both CA- and HA-MRSA isolates. These findings emphasize the growing threat of CA-MRSA and the importance of integrated surveillance of both resistance and virulence in S. aureus populations.

The role of routine terminal ileal intubation (TII) in asymptomatic patients undergoing colonoscopy for colorectal cancer (CRC) screening or post-polypectomy surveillance is debated. While considered a quality indicator in some settings, its clinical utility in this population remains unclear. This systematic review and meta-analysis aimed to evaluate the diagnostic yield, clinical utility and procedural impact of routine TII in patients undergoing CRC screening or post-polypectomy surveillance. We conducted a systematic search of PubMed and Embase up to September 2025, according to PRISMA guidelines. We included studies reporting TII diagnostic yield in asymptomatic adults undergoing CRC screening or post-polypectomy surveillance colonoscopy. Data were synthesized using random-effects models. The primary outcome was the overall diagnostic yield of TII. Secondary outcomes included the diagnostic yield for clinically significant findings, Crohn's disease, and the impact of TII on procedure duration. Eleven studies involving 25659 patients, of whom 13672 underwent TII, were included. The pooled overall diagnostic yield for any ileal finding was 1.74% (95%CI 1.18%-2.57%), with most abnormalities being non-specific and not requiring clinical action. The diagnostic yield for clinically significant pathology was substantially lower at 0.28% (95%CI 0.07%-1.05%), while the yield for detecting Crohn's disease was only 0.1% (95%CI 0.02%-0.44%), corresponding to one case per 1000 ileoscopies during colonoscopy for CRC screening. Routine TII in asymptomatic patients undergoing screening or surveillance colonoscopy provides a negligible diagnostic yield for clinically significant pathology, including Crohn's disease. Our findings do not support performing routine TII during colonoscopy in this patient population.

Abstract Introduction: Neoadjuvant chemotherapy (CT) with pembrolizumab (P) is standard for most patients (pts) with high-risk early TNBC. Biomarkers for the addition of P to CT are lacking. The prognostic and predictive value of TILs in pts who receive neoadjuvant CT+P vs CT alone and the significance of change in TILs from pre- to post-treatment samples remains unclear. Methods: From the prospective DFCI Multicenter TNBC Registry, pts with stage I-III TNBC who received neoadjuvant CT or CT+P were identified. Stromal TILs were scored in tumor samples at baseline (BL) and surgery (if residual disease, RD). TILs were evaluated as a continuous and binary variable using a threshold selected based on BL distribution. Fisher’s exact test was used to compare TILs between CT and CT+P, and between RCB groups. Association with pathologic complete response (pCR) and with recurrence-free (RFS), distant recurrence-free (DRFS) and overall survival (OS) were evaluated using logistic regression and Cox proportional hazards models, respectively, adjusting for clinical stage and neoadjuvant treatment. All statistical tests were two-sided (significance p < 0.05). Results: Between 5/2019-1/2024, 121 TNBC pts were identified; 18 (14.9%) stage I, 49 (40.5%) stage II, 52 (43.0%) stage III, 2 (1.7%) unknown. 19 (15.7%) had germline BRCA1/2 mutations. 49 (40.5%) received CT and 72 (59.5%) CT+P, with anthracycline-based CT in 40 (81.6%) and 62 (86.1%) pts, respectively. The pCR rate was 51.0% (25/49; 95% CI 36.3-65.6%) with CT alone and 58.3% (42/72; 95% CI 46.1-69.8%) with CT+P. Median follow-up was 2.2 years (interquartile range [IQR] 1.4-3.9): CT, 4.2 years (IQR 3.4-5.1); CT+P, 1.7 years (IQR 1.2-2.2). 115 pts had TILs scored at BL and 41 at RD, of whom 35 had paired samples. BL TILs (range 0-90%) were categorized by quartiles (5%, 10%, 30%) with 10% used for primary analysis. Both BL and RD TILs did not differ between CT vs CT+P as a continuous variable (BL p=0.11; RD p=0.56) or ≥10% cutoff (BL p=0.62; RD p=0.56). High BL TILs (≥ 10%) were significantly associated with pCR and this did not differ by treatment (interaction p=0.36). No association was observed between TILs (at BL or RD) and RCB class (TILs as continuous variable: BL p=0.36, RD p=0.84; or 10% cutoff: BL p=0.31, RD p=0.86). High BL TILs (≥ 10%) were associated with longer RFS (aHR 0.15, p=0.01), DRFS (aHR 0.17, p=0.01) and OS (aHR 0.19, p=0.05; or as a continuous variable, aHR per 5-unit increase 0.46, p=0.05). Neither TILs in RD nor increase from BL to RD (in 14/35 pts, 40%) were associated with RFS, DRFS or OS. Conclusion: In this multicenter TNBC cohort, BL TILs were reinforced as a prognostic marker for pCR, regardless of the addition of P to CT. TILs at RD and changes during neoadjuvant therapy were not prognostic. Additional follow-up for survival outcomes is ongoing. Citation Format: R. S. Lee, Q. Jin, B. Binboga Kurt, B. Koca, J. Gomez Tejeda Zanudo, A. Patel, A. Barkell, J. Baginska, O. M. Cunningham, C. E. Stever, T. S. Parker, T. Rahman, M. Luo, I. G. Martino, B. M. Drummey, S. A. Virani, K. Santos, J. Bsat, C. Snow, N. Tung, S. Lo, M. G. Faggen, N. Sinclair, N. Ahmad, M. Constantinou, S. Sinclair, J. L. Meisel, S. A. Kirschner, T. A. King, R. Salgado, E. A. Mittendorf, N. U. Lin, N. Tayob, E. P. Winer, E. C. de Bruin, S. M. Tolaney, A. Moeini, A. C. Garrido-Castro. Association of tumor-infiltrating lymphocytes (TILs) with outcomes in patients with early TNBC treated with neoadjuvant chemotherapy with or without pembrolizumab [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-18.

This study evaluated the extent to which the sleep is disrupted by nighttime awakenings in urban children with and without asthma and examined racial/ethnic differences in sleep outcomes. Three hundred and seventy-nine urban children aged 7 to 9 years with (n = 250) and without (n = 129) asthma were included. Participants were 45% Latino, 34% black, and 21% non-Latino white (NLW). Nighttime awakenings were assessed via actigraphy. Asthma status was assessed by a clinically and via self-report. Children with asthma had significantly more awakenings than those without. Latino children with asthma had more and longer awakenings compared to Latino children without asthma; these effects were not observed among black or NLW participants. Poor asthma control was associated with more awakenings. Urban children face higher risks for poor sleep and asthma outcomes. Multicomponent interventions addressing asthma management and culturally tailored sleep hygiene strategies are necessary to improve asthma and sleep outcomes in this highly burdened population.

Abstract Background Patients with multiple myeloma are at higher risk for infections due to disease pathophysiology and administered therapies. The purpose of this study was to estimate the incidence of invasive fungal infections in patients with multiple myeloma who received B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy.Cumulative incidence rate of IFD among patients with multiple myeloma who received BCMA–directed CAR T-cell therapyCumulative incidence rate of invasive aspergillosis among patients with multiple myeloma who received BCMA–directed CAR T-cell therapy Methods We searched PubMed and EMBASE for studies that included patients with multiple myeloma who received BCMA–directed CAR T-cell therapy and evaluated the incidence of infections among this patient population. We present the pooled cumulative incidence of invasive fungal disease (IFD), invasive fungal aspergillosis, and invasive fungal candidiasis by performing a random-effects meta-analysis. Results After screening 232 citations and excluding studies which did not report infectious complications or with a follow up of less than 30 days, we identified and analyzed studies reporting IFD, invasive aspergillosis, or invasive candidiasis among participants with multiple myeloma who received BCMA-directed CAR T-cell therapy. Specifically, we retrieved 9 studies that reported data on the development of IFD and among 823 patients who received BCMA-directed CAR T-cell therapy, we found that 31 patients developed IFD with a cumulative incidence of 3.19% (95% CI, 1.86-4.79). In addition, we retrieved 7 studies that reported data on the development of invasive aspergillosis, among 515 patients who received BCMA-directed CAR T-cell therapy 9 patients developed invasive aspergillosis with a cumulative incidence of 1.22% (95% CI, 0.21-2.77). For invasive candidiasis, we retrieved 7 studies and among 515 patients who received BCMA-directed CAR T-cell therapy 4 patients developed invasive candidiasis with a cumulative incidence of 0.51 (95% CI, 0.00-1.67). Conclusion In this first meta-analysis evaluating the incidence of IFD in patients with MM receiving BCMA-targeted CAR T-cell therapy, we found that this patient population faces a discernible burden of IFD, including aspergillosis and candidiasis. Although these infections remain relatively uncommon, considerable morbidity and mortality among this patient population supports the need for prospective studies aimed at identifying risk factors. Disclosures Eleftherios Mylonakis, MD, PhD, Chemic Labs/Koda Therapeutics, LLC: Grant/Research Support|Lumen: DSMB|NIH/NIAID: Grant/Research Support|Sciclone: Grant/Research Support|Shionogi: Advisor/Consultant|Synexis: Clinical trial