Citations

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hematopoietic Cell Transplantation (HCT) provide expert, multidisciplinary recommendations for autologous and allogeneic HCT based on current evidence. The NCCN Guidelines focus on pretransplant recipient evaluation, hematopoietic cell mobilization, conditioning, and the diagnosis and management of graft-versus-host disease (GVHD), a common complication of allogeneic HCT that is associated with significant morbidity. This selection from the NCCN Guidelines for HCT focuses on the diagnosis, workup, and management of acute and chronic GVHD, as well as important supportive care considerations.

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT. Results Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35–11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia. Conclusions With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.

ABSTRACT Background Magnetic resonance elastography (MRE) has demonstrated potential in characterizing intracranial tumors, including glioblastoma. The influence of pathology on measurement consistency and interobserver agreement needs evaluation to promote MRE implementation as a quantitative biomarker. Purpose To assess repeatability and interobserver agreement of absolute and normalized magnitude of the complex shear modulus (| G *|), storage modulus ( G ′), and loss modulus ( G ″) in glioblastoma. Study Type Prospective. Population Thirteen adults (5 male, 8 female, mean age 66.23 years) with histopathologically confirmed glioblastoma. Field Strength/Sequence 3 T MRI, modified single‐shot spin‐echo echo‐planar imaging. Assessment Two same‐session MRE acquisitions were performed with patient repositioning. The solid tumor component was independently segmented by 2 observers on contrast‐enhanced T1‐weighted images co‐registered to MRE maps. Statistical Tests Repeatability was assessed using the repeatability coefficient, coefficient of variation, and Bland–Altman plots, and interobserver agreement by the intraclass correlation coefficient. The Wilcoxon signed‐rank test compared parameters and coefficients of variation between tumor‐normal‐appearing white matter and absolute and normalized measurements. Significance was set at 0.05. Results Tumor | G *| and G ′ showed repeatability coefficients of 0.07–0.08 kPa and 0.05 kPa, compared with 0.13 kPa (| G *|) and 0.15–0.16 kPa ( G ′) for normalized measurements. Coefficients of variation in tumor regions were 1.42% ± 1.12%–1.60% ± 1.41% for | G *| and 1.19% ± 0.96%–2.08% ± 2.22% for G ′, significantly lower than normalized values (4.82% ± 4.49%–4.21% ± 4.27% for | G *|; 5.12% ± 5.04%–5.45% ± 4.53% for G ′). Tumor | G *| and G ′ showed excellent interobserver agreement (intraclass correlation coefficients 0.97 and 0.95). Tumor G ″ demonstrated higher variability than | G *| and G ′ (coefficients of variation 8.58% ± 7.69%–7.51% ± 6.73%), with no significant difference between absolute and normalized measurements ( p = 0.14). Data Conclusion Tumor | G *| and G ′ are the most repeatable metrics in glioblastoma. Normalization reduces measurement repeatability due to normal‐appearing white matter variability. The small sample size ( n = 13) limits generalizability. Evidence Level 2. Technical Efficacy Stage 2.

Introduction: An 83-year-old female was discovered to have an incidental circumferential duodenal adenoma by upper endoscopy after being evaluated for irritable bowel syndrome. Imaging revealed a dilated common bile duct and main pancreatic duct but no evidence of malignancy. Therefore, she was considered a candidate for surgical removal. Methods and Materials: Using robotic-assisted surgery, a 4 trocar approach was employed involving three 8-mm and one 12-mm robotic trocar apart. 1 A standard cholecystectomy followed by careful dissection of the duodenum from the pancreas head was performed. The ampulla was identified, and the duodenum was laterally retracted with transection of the identified ampulla with exposure of the pancreaticobiliary orifice. A two-layered duct to mucosa pancreaticobiliary anastomosis was established between the common bile, pancreatic duct, and the jejunum. A side-to-side stapled gastrojejunostomy was constructed and the operation concluded. 2 , 3 Results: Pathological analysis revealed a noninvasive polypoid lesion within the duodenum measuring 7.5 × 5.0 × 0.6 cm. The surgery was completed in 350 minutes with blood loss of 100 mL. There were no postop complications, and the patient was discharged on the fifth day. The patient had some gastric symptoms post discharge which subsided with time. Conclusions: This case highlights the feasibility and safety of robotic resection for an obstructing duodenal polyp in complex anatomical regions, demonstrating its clinical utility and relevance for the management of benign ampullary duodenal lesions. Patient Consent Statement: The patient who was operated upon issued consent for operative data to be used for publication, under Mayo Clinic, Jacksonville, signed consent forms. The author(s) have received and archived patient consent for video recording/publication in advance of video recording of procedure. Conflict of Interests: This article is not under consideration by any other journal, and all authors have approved the article. None of the authors have any competing financial interests. Runtime of video: 9 minutes and 33 seconds.

BACKGROUND The use of Mohs micrographic surgery as a treatment for melanoma is rising, but the reliability of Mohs surgeons in assessing MART-1 melanoma en-face margins has not been evaluated. OBJECTIVE To evaluate interrater and intrarater reliability of Mohs surgeons in interpreting margins of early-stage melanoma. METHODS Twenty Mohs surgeons were asked to independently review images of frozen section MART-1 en-face peripheral margins of in situ or early-stage melanoma. Surgeons determined margins as positive or negative at initial evaluation and 6 weeks later. Primary outcomes were interrater and intrarater reliability. RESULTS Interrater agreement was 84.1% (95% confidence interval [CI]: 75.5%–92.8%) for assessment 1 and 87.5% (95% CI: 78.4%–96.4%) for assessment 2, with kappa values 0.68 (95% CI: 0.50–0.82) and 0.75 (95% CI: 0.57–0.88). Average intrarater percent agreement was 95.0% (95% CI: 70.6%–100.0%) with average kappa 0.90 (95% CI: 0.50–1.00). CONCLUSION Substantial interrater and nearly perfect intrarater agreement was identified among surgeons assessing melanoma margins utilizing MART-1 immunostaining, demonstrating consistent and reproducible assessment of melanoma margins during Mohs cases.

Abstract Aberrant DNA methylation and copy-number alterations (CNA) drive Barrett’s esophagus progression to esophageal adenocarcinoma; however, their combined utility for early detection is unclear. We aimed to identify and validate methylated DNA markers (MDM) and CNAs to distinguish esophageal adenocarcinoma/high-grade dysplasia (HGD) from nondysplastic Barrett’s esophagus (NDBE). In this multiphase, multicenter study, we discovered and validated MDMs and quantified CNAs utilizing whole-genome methylation sequencing of esophageal brushings. DNA biomarkers identified from discovery were further validated in independent patients with paired esophageal brushing and swallowed capsule sponge samples. MDMs were filtered against a reduced representation bisulfite sequencing dataset obtained from independent tissue samples to advance only concordant candidates. CNA burden was quantified using ichorCNA-derived aneuploidy scores (AS). Two hundred MDMs discovered in HGD (N = 18) and esophageal adenocarcinoma (N = 18) versus NDBE brushing samples (N = 18) were tested in independent samples (N = 146). A 52-MDM panel achieved a cross-validated AUC of 0.88 [95% confidence interval (CI), 0.82–0.95]; the addition of AS improved discrimination of HGD/esophageal adenocarcinoma from NDBE to 0.91 (95% CI, 0.86–0.97) AUC. At 80% specificity, the combined model detected 93% of esophageal adenocarcinoma and 88% of HGD cases. In paired capsule sponge samples, a 58-MDM panel achieved a cross-validated AUC of 0.77 (95% CI, 0.66–0.88); a combined 58-MDM and AS model achieved AUC 0.80 (95% CI, 0.7–0.9). MDMs and AS discerned HGD/esophageal adenocarcinoma from normal esophagus/NDBE in endoscopic brushing and capsule sponge samples. This approach may improve Barrett’s esophagus surveillance. Prevention Relevance: This study demonstrates that combining epigenetic and genomic biomarkers across minimally invasive sampling methods can accurately distinguish HGD/esophageal adenocarcinoma from nondysplastic Barrett’s esophagus, offering promising, less invasive strategies to improve BE surveillance and enable endoscopic therapy for esophageal adenocarcinoma prevention and treatment.

Abstract Nephrotic syndrome is a rare, heterogeneous kidney disorder characterized by proteinuria, hypoalbuminemia, and edema. To elucidate its genetic architecture, we conducted a large-scale, electronic health record (EHR)-linked, multi-ancestry genome-wide association study comprising 5,214 cases and 1,601,060 controls. We identified 37 distinct loci associated with disease risk, including novel associations at JAML and STPG2 , and confirmed prior signals at PLA2R1 , HMCN1 , and APOL1 . Fine-mapping of the major histocompatibility complex (MHC) revealed the strongest association at DRB103:01:01G in individuals of European ancestry (OR = 2.01, P = 1.4×10⁻²⁰), alongside nominal ancestry-specific associations in African ( DOA01:01:05 ) and Latino ( DPB1*14:01:01G ) populations. Transcriptome-wide association analysis (TWAS) identified 484 significant gene-tissue associations, including C4A in kidney cortex. Expression quantitative trait locus (eQTL) mapping revealed numerous cis-eQTLs in glomerular and tubular renal tissues, largely within the MHC region. We observed significant genetic correlation between adult and pediatric nephrotic syndrome (Rg = 0.63, P = 3.5x10 -11 ), suggesting shared genetic etiology. Pathway analyses implicated estrogen receptor signaling and histone modification. Mendelian randomization implicated APOM expression and apomorphine exposure with increased disease risk (OR = 4.93, P = 1.8x10 -19 ). These results expand the understanding of nephrotic syndrome pathogenesis and highlight ancestry-informed targets for therapeutic development.

Background Whistal (Whipple + Distal) is a rare parenchyma-preserving technique for select patients with disease in both the pancreatic head and tail, sparing a disease-free middle segment. It may also be used after prior partial pancreatectomy. Surgical resection remains the cornerstone of treatment for pancreatic diseases such as PDAC, RCC metastasis, and multifocal IPMN. Whistal may balance oncologic control with pancreatic function preservation. Though infrequent, it is practiced and reported in literature. Methods With IRB approval, a retrospective review of a prospective database (Aug 1999-Mar 2024) identified Whistal cases, categorized as staged Whistal (SW) or concomitant whistal (CW). Perioperative outcomes were assessed via Clavien-Dindo and ISGPS. A PubMed search identified reported middle segment pancreatectomy (Whistal) cases. Results Of 2008 resections (Aug 1999-Mar 2024), 5 were Whistals (3 CW, 2 SW) for PDAC (n = 3), RCC (n = 1), IPMN (n = 1), and bile duct stricture (n = 1). Rates for major morbidity, POPF, and DGE were each 40%. Literature review found 26 papers reporting 52 additional Whistal cases. Conclusion Whistal is safe for select patients, but wider adoption and long-term data are needed to confirm its efficacy.

Despite efforts to improve donor heart allocation policies, geographic disparities, logistical challenges and patient criteria limit organ availability. However, recent surgical innovations offer potential solutions. These include partial heart transplantation and xenotransplantation. Partial heart transplantation is a new procedure with the potential to address several clinical challenges in treating congenital heart defects. Cardiac xenotransplantation involves the transplantation of genetically modified porcine hearts into humans, offering a potential solution to the shortage of donor organs. Although immunologic barriers and ethical concerns remain, ongoing research aims to mitigate the risks and optimize outcomes, providing hope for patients in need. These innovative surgical approaches offer promising avenues for addressing the critical shortage of donor hearts and with ongoing research, may hold the potential to revolutionize heart transplantation, and improve outcomes for patients facing terminal heart failure.

Abstract The environmental impact of computer-aided diagnosis (CADx) in colonoscopy is unknown. The potential to reduce greenhouse gas emissions by limiting unnecessary polypectomies may be offset by emissions associated with CADx devices. We quantified and compared the carbon footprint of colonoscopy with and without CADx. Life-cycle carbon emissions associated with endoscopic snares, polyp traps, histopathology, and CADx devices were estimated using life-cycle assessment software. The effect of CADx was estimated by the carbon dioxide equivalent (CO2e) emissions related to outcomes from a prospective cohort of patients who underwent colonoscopy with optical diagnosis under a leave-in-situ strategy (i.e. rectosigmoid polyps ≤5 mm predicted as non-neoplastic were not removed) with and without CADx assistance. We analyzed 1134 individuals (median age 67 years, 59% male) with 1716 colorectal polyps. Colonoscopy with CADx reduced the number of snares and polyp traps from 567 to 543 (difference: 24) and histopathology submissions from 1343 to 1278 (difference: 65). However, the total carbon footprint increased from 832 kg CO2e (95%CI 815 to 847) without CADx to 946 kg CO2e (95%CI 927 to 965) with CADx, corresponding to an absolute increase of 114 kg CO2e (95%CI 80 to 150) or 0.10 kg CO2e per colonoscopy. Using CADx under a leave-in-situ strategy increased the environmental burden of colonoscopy.