Faculty Bibliography

Rapid molecular assays guiding treatment of methicillin-resistant Staphylococcus aureus (MRSA) detect SCCmec (Xpert) or the SCCmec-orfX junction (BCID2). Sequence variation in this region can disrupt primer binding, yielding false-negative results. Investigation of a missed bloodstream infection linked escape to a CRISPR-Cas-associated SCCmec variant, leading to identification of 64 variants from 45 patients-2% of 2,432 screened. Misdiagnosis was restricted to clonal complex 5, a hospital-associated lineage; 11 of 40 SCCmec/junctions evaded detection by BCID2 or Xpert. Variants had mecA instability and circulated in healthcare settings. Our findings reveal a unique escape mechanism and underscore a threat to diagnostic accuracy.

After decades of efforts by academic and professional organizations and by governmental agencies to promote advance care planning, less than half of adults in the USA have formally executed advance directives. For patients who have completed these documents, studies find limited impact on end-of-life care. In this paper, we discussed ways in which bias towards certain values in the health care enterprise including ethnocentrism, the centering of one set of cultural norms, may contribute to the public's ambivalence and the relative inefficacy of advance directives. We offer a more expansive perspective on this aspect of clinical care with the goal of serving all patients more effectively.

Methotrexate (MTX) has improved survival for children with acute lymphoblastic leukemia, but is associated with a 3%-7% incidence of neurotoxicity. This retrospective study showed a higher incidence of MTX neurotoxicity (11.3%) with the classic presentations of stroke-like syndrome (17/19), seizures (2/19), and the majority (14/19) showing characteristic radiographic findings. Most cases occurred during the consolidation phase, a median of 6 days after MTX exposure. Older age, Hispanic ethnicity, greater body mass index, and National Cancer Institute high-risk status were predictors of neurotoxicity, with only ethnicity remaining significant in adjusted analyses. Prophylactic leucovorin after repeated intrathecal MTX doses may be protective.

BACKGROUND:The "July Effect" refers to the potential increase in adverse outcomes associated with the annual turnover of medical trainees, though its impact on surgical fields remains uncertain. Additionally, few studies have examined whether the operative day of the week and subsequent flap monitoring during the weekend affect time to reoperation or flap salvage. This study investigated whether academic quarter and operative day influence reoperation rates, flap salvage, or flap failure in microvascular free flap procedures. METHODS:A retrospective review was conducted on 769 free flaps performed between June 2011 and November 2023. Multivariate analyses adjusted for patient demographics, comorbidities, flap type, and recipient region. Flaps were categorized by academic quarter and operative day, excluding weekends due to limited sample size. Primary outcomes included reoperation rates for vascular compromise, time to reoperation, and flap salvage. RESULTS:No significant differences in reoperation rates for vascular compromise were observed across academic quarters. While procedure duration trended longer in the first three quarters compared to the fourth, these differences were not statistically significant. Additionally, operative day did not impact reoperation rates, flap salvage, or time to reoperation. Flaps were predominantly indicated for head and neck reconstruction (74.4%) and had an overall flap loss rate of 3.0%. CONCLUSION/CONCLUSIONS:We found no evidence of a "July Effect" in microvascular surgery or that operative day affects free flap outcomes. Institutional factors, such as structured flap monitoring, attending oversight, and advanced practice provider support, likely mitigate risks associated with trainee turnover and shift-based staffing fluctuations.

Atherosclerotic cardiovascular disease is a major contributor to the global disease burden. Atherosclerosis initiation depends on cholesterol accumulation in subendothelial macrophages (Mφs). To clarify the role of Bmal1 in Mφ function and atherosclerosis, we used several global and myeloid-specific Bmal1-deficient mouse models. Myeloid-specific Bmal1-deficient mice had higher Mφ cholesterol and displayed greater atherosclerosis compared with controls. Bmal1-deficient Mφs exhibited: (a) elevated expression of Cd36 and uptake of oxLDL; (b) diminished expression of Abca1 and Abcg1, and decreased cholesterol efflux and reverse cholesterol transport; and (c) reduced Npc1 and Npc2 expression and diminished cholesterol egress from lysosomes. Molecular studies revealed that Bmal1 directly regulates basal and cyclic expression of Npc1 and Npc2 by binding the E-box motif (CANNTG) sequence recognized by Bmal1 in their promoters and indirectly regulates the basal and temporal regulation of Cd36 and Abca1/Abcg1 involving Rev-erbα and Znf202 repressors, respectively. In conclusion, Mφ Bmal1 is a key regulator of the uptake of modified lipoproteins, cholesterol efflux, lysosomal cholesterol egress, and atherosclerosis and, therefore, may be a master regulator of cholesterol metabolism in Mφs. Restoration of Mφ Bmal1 expression or blocking of factors that decrease its activity may be effective in preventing atherosclerosis.

Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane's RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review (https://ebipsyche-database.org/). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control (k = 11; SMD=-0.85 [-1.09; -0.60]; I²=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms (k = 8; SMD=-0.62 [-0.97; -0.28]; I²=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMD_MDMA=-1.18 [-2.04; -0.32]; I²=0 %; k = 2; GRADE=low and SMD_serotonergic=-0.88 [-1.70; -0.06]; I²=54 %;k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates (k = 6; RR=1.42 [0.89; 2.26]; I²=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms (k = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RR_MDMA=0.74 [0.32; 1.72]; RR_serotonergic=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.

BACKGROUND AND AIMS/OBJECTIVE:Prophylactic colonic endoscopic submucosal dissection (ESD) defect closure may reduce delayed adverse events (DAEs) such as bleeding and perforation associated with ESD and facilitate same day discharge. We compared the effect of colonic ESD defect closure (closed group) with no closure (open group) on DAEs and overnight hospital admission. METHODS:We performed a Western multicenter retrospective study on patients who underwent colon ESD. Rectal lesions were excluded. DAEs were defined as adverse events within 2 weeks of ESD. Primary outcome measures were DAEs and overnight hospital admission. Multivariate analyses were performed. RESULTS:560 patients underwent colon ESD and 364 (71.8%) patients had complete defect closure. Closed group had a significantly lower rate of delayed bleeding (1.7% vs 5.6%, p = 0.03) compared to open group. Multivariate analysis with adjusted odds ratios (aOR) revealed right sided polyps (aOR = 7.0) and anticoagulation/antiplatelet agents (aOR = 6.6) increased the risk while defect closure (aOR = 0.2) decreased the risk of delayed bleeding. Defect closure amplified the reduction in risk of delayed bleeding (2.4% vs 10.4%, p = 0.014) for right-sided polyps. Malignant polyps significantly increased the risk of delayed perforation (aOR = 3.3) and overnight hospitalization (aOR = 2.9). Defect closure (aOR = 0.6), traction use (aOR = 0.6) and topical hemostatic agent use (aOR = 0.4) significantly reduced the risk of overnight hospitalization. CONCLUSION/CONCLUSIONS:Prophylactic closure of colon ESD defects was associated with a significant reduction in delayed bleeding with number needed to treat (NNT) of 25.6 (especially for right sided polyps, NNT 12.5), and post-procedural overnight hospitalization. Prospective studies are needed to further validate these results.

IMPORTANCE/UNASSIGNED:Repeating a prostate-specific antigen (PSA) test after an elevated measurement is a guideline-recommended component of the prebiopsy workup. However, it is unclear whether certain patients can be exempted from repeat PSA testing and proceed directly to further workup. OBJECTIVE/UNASSIGNED:To determine yearly PSA variability and implications of repeating an elevated PSA in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective multicenter cohort study used data from men aged 54 to 75 years participating in the screening arm of the randomized PLCO trial who received PSA testing annually over 6 years (between 1995 and 2006) without a prostate cancer diagnosis. Data were analyzed from February 10, 2023, to May 23, 2025. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was the proportion of PSA measurements above 1 of the 3 biopsy thresholds of interest (2.5, 3.0, and 4.0 ng/mL) that decreased below the threshold at the subsequent yearly measurement. Analyses were conducted at both the PSA test and patient levels. RESULTS/UNASSIGNED:Among 11 176 eligible patients (median age 60 years, IQR, 57-65 years), 2700 patients were included at a threshold of 2.5 ng/mL, 1928 patients at 3.0 ng/mL, and 952 patients at 4.0 ng/mL at least once. Among PSA measurements greater than or equal to 2.5 ng/mL, 22% (95% CI, 21%-23%) decreased below 2.5 ng/mL the following year; rates were similar for thresholds of 3.0 ng/mL and 4.0 ng/mL. At the patient level, 54% (95% CI, 53%-56%) of men with at least 1 PSA greater than or equal to 2.5 ng/mL had a subsequent level below this threshold, with slightly greater rates for the higher thresholds. A predictive scoring system incorporating current and prior PSA levels showed that patients with PSA levels persistently above thresholds had a low (<10%) probability of PSA decreasing below the threshold. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, significant intra-individual variability in PSA levels was observed in this large screening cohort, with many elevated values falling below the threshold at the next yearly measurement. These findings suggest the utility of guideline recommendations to confirm elevated PSA results in most patients before performing further diagnostic evaluation and that patients with a prior PSA score above a given biopsy threshold, and no recent PSA scores below that threshold, could proceed to further diagnostic evaluation without repeat testing.

Malignancy associated with ileal neobladders or ileal conduits in postradical cystectomy patients is rare. Yet, recurrent urothelial carcinoma or new primary cancers, such as adenocarcinoma, enteric type (EA), are potential complications that pose significant clinical challenges. This study aimed to evaluate the incidence, clinical outcomes, and management strategies for malignancies in patients with ileal neobladders or ileal conduits. A retrospective review was conducted at 3 large academic institutions, identifying 10 cases of malignant tumors arising in ileal neobladders or ileal conduits over a period of 10 years. The study cohort included 9 male and 1 female patient aged 56 to 92 years (mean age = 68.2 y). Data on clinical presentation, management, pathology, and outcomes were collected, with a focus on recurrence and disease-specific survival rates. Seven of 10 patients (all males) were initially diagnosed with invasive high-grade urothelial carcinoma (IHGUC), whereas 3 patients had a history of bladder augmentation with colonic tissue (BA) for benign etiologies. Of patients with IHGUC, 2 patients received neoadjuvant chemotherapy, 1 received a combination of chemotherapy agents, and 3 patients underwent intravesical BCG therapy. All IHGUC exhibited conventional morphology without divergent differentiation. Pathologic staging of the cystectomy for IHGUC ranged from pTa to pT3a, with 4 cases showing lymph node metastasis. IHGUC recurrence was detected in 6 of 7 patients with a latency period range of 7 months to 6.7 years (mean 37 mo) and all tumors again exhibiting conventional morphology without divergent differentiation. IHGUC recurrence demonstrated a pathologic stage ranging from pT2 to pT4, and 5 died (mean = 4.2 mo), whereas 1 patient remains alive and on surveillance. EA occurred in 4 patients, including 3 BA patients and 2 foci in 1 patient with a neobladder for IHGUC. Staging of patients with EA ranged from pTis to pT2 developing 31 to 55 years postsurgery. Three of 5 EA cases were associated with a precursor lesion including 2 tubular adenoma with high-grade dysplasia, and 1 sessile serrated lesion with dysplasia. EA patients had relatively favorable outcomes compared with IHGUC patients,  with all surviving patients currently on surveillance though with one case demonstrating nodal metastasis. Although rare, malignancies in ileal neobladders or ileal conduits are a serious complication. Although IHGUC recurrence often leads to poor survival, EA patients-especially those with prior bladder augmentation-seem to be associated with better survival outcomes. The long latency period for IHGUC recurrence and the favorable prognosis for EA underscore the need for vigilant long-term surveillance.