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Introduction: Post-operative atrial fibrillation (POAF) affects up to 40 percent of coronary artery bypass graft (CABG) patients and is associated with stroke, prolonged hospitalization, and increased mortality. POAF typically occurs between one and six days after ICU admission, peaking on postoperative day two. Early identification of at-risk patients remains an unmet need. We hypothesized that frequency-domain heart rate variability (HRV) metrics derived from ECG waveforms within 24 hours of ICU admission can be used to distinguish patients who later develop POAF by detecting early autonomic imbalance. Methods: With IRB approval, we retrospectively analyzed de-identified ECG waveform data from 58 post-CABG patients monitored in a cardiac ICU via a Predictive Analytics Platform (Nihon Kohden Digital Health Solutions, Irvine, CA). HRV metrics were extracted from one-hour ECG segments during the first 24 hours of ICU admission. R-waves were detected using a modified Pan-Tompkins algorithm and verified for sinus rhythm. R-R intervals were resampled using PCHIP interpolation. Frequency-domain metrics including low-frequency (LF percent), high-frequency (HF percent), and LF to HF ratio were computed using the Welch method. Differences between POAF and non-POAF groups were evaluated using Wilcoxon rank-sum tests. Results: POAF occurred in 22 of 58 patients (38 percent) between days 1 and 6, with a mean onset of 2.2 days. Compared to those without POAF, affected patients had significantly lower LF percent (64.1 vs. 86.8, p = 0.004), higher HF percent (35.9 vs. 13.2, p = 0.004), and a lower LF to HF ratio (1.8 vs. 6.6, p = 0.004). Mean R-R intervals were not significantly different (p = 0.831), supporting autonomic imbalance rather than heart rate as a differentiator. Conclusions: Frequency-domain HRV metrics obtained early in the ICU course are associated with subsequent POAF, revealing autonomic signatures in advance of arrhythmia onset. These robust, scalable metrics are suitable for real-time implementation and support HRV-based early warning models for post-CABG patients.

Prognosis of metastatic pancreatic cancer remains poor. KRAS mutations are common in pancreatic cancer and are an attractive therapeutic target. Based on a next-generation mechanistic dynamic model, we hypothesized that a combination of type I½ RAF inhibitor (vemurafenib) and type II RAF inhibitor (sorafenib) would have clinical activity in KRAS-mutated advanced pancreatic cancer. We conducted an open-label pilot phase II trial of vemurafenib and sorafenib combination in advanced pancreatic cancer with KRAS mutations. Eligible patients had progressed on two or more prior treatment regimens, had adequate performance status, adequate organ function and measurable disease, and were able to swallow oral medication. The primary objective was disease control rate (partial or complete response or stable disease ≥ 16 weeks). Secondary objectives included safety, progression-free (PFS) and overall survival (OS), and changes in plasma phospho-ERK and phospho-AKT. Nine patients with KRAS-mutated pancreatic cancer were enrolled. The median age was 62.8 years and the median prior lines of treatment was 3. Four of the initial five patients had treatment interruption due to adverse events, and the subsequent four patients were treated at a reduced dose. Three grade 3 adverse events were reported and included anemia (n = 1), hypophosphatemia (n = 1), and maculopapular rash (n = 1); rash and anemia were deemed treatment related. Disease control rate was 0%. Median PFS was 1.6 months (95% CI, 0.5-not available), and median OS was 2.9 months (95% CI, 0.6-5.4). Compared to baseline, the best response for relative plasma phospho-ERK levels were -39 to +11% and -32 to +49% for plasma phospho-AKT levels. The combination of vemurafenib and sorafenib in KRAS-mutated refractory pancreatic cancer did not yield disease control in this pilot phase II study. The lack of clinical efficacy may be due to inadequate inhibition of RAS-to-ERK signaling as toxicities necessitated dose reduction. NCT05068752.

Background: We often identify our vocation with a calling. Pediatric neurosurgeons are vulnerable to burnout and moral injury given the high emotional stakes, relentless pursuit of precision, and the enduring demands of patient care. Physician wellness is a prerequisite for safe, high-quality care, and professional longevity. Summary: This article highlights physician wellness as a critical issue in pediatric neurosurgery, explores the public health crisis of physician suicide and burnout, and outlines strategies to sustain performance and resilience through relationships, purpose, and self-compassion. Key Messages: In this narrative reflective article, we make recommendations based on our personal experience and on the belief that wellness is not optional – it is essential to fulfill our calling as healers.

Abstract BACKGROUND ACPs are brain tumors that typically originate in the suprasellar region and are associated with significant morbidity, with patients experiencing visual impairment, pituitary dysfunction and headaches. No systemic therapies are available for ACP, while surgery or radiation can be challenging and result in complications. Almost all ACPs have Wnt pathway-activating mutations (WPAMs), predominantly CTNNB1 activating mutations. FOG-001 is a Helicon™ peptide that competitively inhibits the interaction between β-catenin and TCF transcription factors in the Wnt-signaling pathway. Here we report safety and preliminary efficacy of FOG-001 in ACP patients. METHODS This is a first-in-human, phase 1/2, multicenter study of FOG-001 in patients with WPAM+ solid tumors, treated at doses ranging from 36-480 mg/m2 (NCT05919264). Patients with histologically confirmed, locally-advanced ACP are eligible. Disease assessments, per RECIST v1.1, are performed every 8 weeks for 48 weeks and every 12 weeks thereafter. Primary objective is safety and tolerability of FOG-001. Secondary objective is anti-tumor activity. RESULTS As of May 11, 2025, 3 ACP patients have received FOG-001 monotherapy at doses of 144 mg/m2 (n=1) and 360 mg/m2 (n=2). All patients are male and median age is 42 years (range 19-62). All patients had prior surgery and 1 received radiation. All treatment-related adverse events (TRAEs) were low-grade (no Grade ≥3 TRAEs). The most common TRAEs were hyponatremia (n=2) and thrombocytopenia (n=2), both reversable. No treatment-related serious adverse events or dose reductions have been reported. Tumor size has decreased in all patients, with one patient achieving a partial response (PR), with a 48.0% reduction, and the other two stable disease (24.0% and 19.2% decrease). CONCLUSIONS FOG-001 has been well tolerated in patients with locally-advanced ACP. All patients have had tumor size reductions, including one PR, suggesting that the Wnt-signaling pathway is an actionable target in ACP.