Divisions AdventHealth (formerly Adventist Health System) is a Christian faith-based, non-profit health care system headquartered in Altamonte Springs, Florida, that operates facilities within twelve states across the United States. The Adventist Health System was rebranded AdventHealth on January 2, 2019. It is the largest not-for-profit Protestant health care provider and one of the largest non-profit health systems in the nation. It operates 50 hospitals in nine states, with over 8,200 licensed beds. It has 1,200 outpatient settings serving more than five million patients annually.
Severe obesity (body mass index ≥ 40 kg/m2 or ≥ 35 kg/m2 with obesity-related comorbidities) is increasingly prevalent and independently associated with elevated perioperative morbidity and inferior oncologic outcomes in patients with colorectal cancer (CRC). Despite these risks, intentional preoperative weight optimization is not routinely incorporated into CRC management, owing to concerns regarding treatment delay, absence of guideline endorsement, and limited supporting evidence. A literature review was conducted using PubMed and Embase to evaluate the impact of severe obesity on morbidity, mortality, and oncologic outcomes in CRC. Peer-reviewed English-language studies involving adult human subjects were included, while conference abstracts, non-English publications, and studies unrelated to obesity and CRC were excluded. In the absence of published reports describing synchronized weight loss and CRC management in patients with severe obesity, three novel retrospective case examples were included to demonstrate feasibility during neoadjuvant treatment, with institutional review board approval obtained for all cases. Severe obesity complicates CRC staging due to limitations in cross-sectional imaging and anatomic delineation. Furthermore, severe and particularly visceral obesity is associated with increased rates of anastomotic leak, surgical site infection, and conversion to open surgery. Current CRC guidelines do not incorporate structured weight-loss strategies into standard treatment algorithms. Metabolic bariatric procedures, such as sleeve gastrectomy, achieve rapid and clinically meaningful weight reduction, often resulting in improved operative exposure and technical conditions for subsequent resection. Pharmacologic therapies, while more broadly accessible and less invasive, typically yield more modest reductions in visceral adiposity. Task force members report early experience across three distinct cases of locally advanced CRC in patients with severe obesity, demonstrating successful preoperative visceral fat reduction through multidisciplinary coordination incorporating metabolic bariatric surgery or pharmacologic therapy during neoadjuvant windows, followed by definitive oncologic resection. Severe obesity adversely influences CRC staging, operative complexity, and perioperative outcomes. Intentional metabolic optimization—through bariatric surgery or pharmacologic therapy—may represent a viable adjunct within multidisciplinary, patient-centered CRC care pathways. However, the absence of prospective short- and long-term outcome data underscores the need for systematic investigation to define optimal timing, safety parameters, and oncologic efficacy of weight-loss interventions in this high-risk population.
Introduction:Adjunct agents in bowel preparation for colonoscopy have the potential to improve procedure outcomes. We performed a systematic review and meta-analysis to investigate the effects of adjunct single-dose linaclotide with bowel prep on colonoscopy outcomes.Methods:We conducted a comprehensive search in PubMed, Embase, Cochrane, and Web of Science from inception until April 2025 for randomized controlled trials comparing single-dose linaclotide adjunct bowel prep and standard bowel prep. Our pooled data was analyzed for adenoma detection rates (ADR), polyp detection rates (PDR), bowel prep quality, adverse reactions, and other secondary outcomes. A random effects model was used, and the data was presented using pooled odds ratios (OR) and mean differences (MD) with 95% CI.Results:Seven manuscripts were included with 2209 patients (1267 in the linaclotide group and 942 in the control group). The linaclotide group had a significantly higher ADR (OR: 1.31, 95% CI: 1.04-1.64, P=0.02, I 2 0%) and PDR (OR: 1.43, 95% CI: 1.13-1.80, P=0.003, I 2 0%). Adequate prep was higher in the linaclotide group among patients with diagnosed constipation (P=0.002). The linaclotide group had a lower incidence of abdominal pain (P=0.0009), bloating (P=0.0006), and sleep disturbance (P=0.002).Conclusion:Linaclotide used as a single dose adjunct to bowel prep before colonoscopy increased ADR and PDR. Adequate prep was higher with linaclotide in patients with diagnosed constipation. Linaclotide also decreased the odds of abdominal pain, bloating, and sleep disturbances.
Accurate size estimation of large (≥ 20 mm) colorectal laterally spreading tumors (LSTs) is essential for procedural planning, risk stratification, and predicting technical difficulty. Yet, the reliability of visual LST size assessment among endoscopists has not been systematically evaluated. 46 LSTs were recorded during colonoscopy. Twenty-four international expert endoscopists independently reviewed de-identified videos and provided visual estimates for (1) maximal diameter, (2) oral–anal axis, (3) left–right axis, and (4) percentage of colonic circumference involved. Each lesion was assessed twice in randomized order. Fleiss’s kappa, Krippendorff’s alpha, and intraclass correlation coefficients (ICC) were used to evaluate inter- and intra-rater agreement. A total of 1104 measurements were collected. Inter-endoscopist kappa agreement for maximal diameter was poor (κ = 0.16), with similarly poor agreement for the oral–anal (κ = 0.15) and left–right axes (κ = 0.14). The percentage of circumferential involvement demonstrated moderate reproducibility (ICC 0.74 and 0.70 across rounds). Subgroup analyses showed consistently poor agreement for larger lesions for diameter-based methods, whereas circumferential percentage estimation ranged from poor to good depending on LST size and morphology. Intra-endoscopist agreement for diameter- and axis-based approaches showed wide variability (κ range 0.01–0.67), while circumferential estimates achieved good to excellent agreement for most endoscopists. Visual estimation of large colorectal LST size is highly variable among expert endoscopists. Maximal diameter and axial lengths demonstrate poor inter- and intra-observer reliability. Circumferential extent is the most reproducible descriptor and may be the preferred approach for reporting LST size in clinical practice and research.
Syndromic craniosynostosis is characterized by premature fusion of one or more cranial sutures, often in association with multisystem anomalies affecting the airway, cardiovascular, musculoskeletal, and neurodevelopmental systems. Variants in genes such as TWIST1 contribute to phenotypic heterogeneity and may influence surgical timing, risk stratification, and long-term craniofacial planning. We present a severe syndromic craniosynostosis phenotype associated with a previously undescribed TWIST1 variant and discuss perioperative considerations of staged cranial vault reconstruction. We report a female infant with craniofacial dysmorphism and multisuture craniosynostosis with complete fusion of the bilateral coronal sutures and widening of the sagittal and metopic sutures. Her phenotype included hypertelorism, frontal bossing, exophthalmos, micrognathia, microtia with aural atresia, cleft palate, and limb anomalies. Additional comorbidities included cardiovascular, respiratory, and feeding abnormalities. Genetic testing revealed a novel TWIST1 missense variant (c.423C > G; p.Asp141Glu), not previously reported in population databases or associated with TWIST1-related disease. Due to progressive dysmorphology and worsening orbital proptosis, early strip craniectomy was performed to permit brain-driven anterior vault expansion. At 8.8 months, PVDO with virtual surgical planning was performed to improve intracranial volume and cranial morphology. The postoperative course was complicated by respiratory failure, cardiac arrest, intracranial abscess, and pseudomeningocele requiring surgical management. This case highlights the expanding genotypic and phenotypic variability associated with TWIST1 alterations. It emphasizes the need for ongoing genetic investigation to delineate pathogenic variants, improve prognostication, and refine surgical planning in complex craniosynostosis.
Buntanetap is an orally available small RNA targeting molecule that inhibits the translation of multiple neurotoxic aggregating proteins, including amyloid precursor protein (APP) and Tau. It has been evaluated in 13 clinical trials involving over 1000 participants, including healthy volunteers, patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has shown a favorable safety and tolerability profile. In two small studies in early AD, buntanetap demonstrated a trend toward cognitive improvement, despite being underpowered for efficacy. In a Phase2/3 study in early PD, it also improved PD patients’ cognitive functions. We evaluated safety and efficacy of buntanetap in treating mild to moderate AD patients in this 3-month randomized double-blind dose-ranging study (NCT05686044). Total of 351 Patients were equally randomized to either 7.5 mg, 15 mg, 30 mg buntanetap or placebo. Buntanetap had a favorable safety profile. The study did not meet its primary endpoints (ADAS-Cog-11 and ADCS-CGIC), as 40% of participants lacked amyloid pathology. However, in amyloid biomarker-positive mild AD patients, buntanetap demonstrated nominally statistically significant dose-dependent cognitive benefits, supported by biomarker evidence of target and pathway engagement. Further evaluation of buntanetap in this patient population are warranted. A Phase 3 trial is currently underway to confirm these findings (NCT06709014).
