Citations

Context.— One objective of the College of American Pathologists/American College of Medical Genetics Cytogenetics Committee is to ensure the accurate detection and clinical interpretation of abnormalities observed by fluorescence in situ hybridization (FISH) analysis when evaluating solid tumor and brain/glioma specimens. Objective.— To report on a 20-year performance summary (2006–2025) of FISH challenges focusing on solid tumor and brain/glioma specimens. Design.— A retrospective review was performed from 2006–2025 to identify FISH challenges specifically addressing solid tumor and brain/glioma specimens. The overall performance of participants was evaluated to identify potential recurring errors. Results.— A total of 54 solid tumor formalin-fixed paraffin-embedded (FFPE) FISH challenges were provided from 2006–2025, including 38 FFPE specimen challenges and 16 educational image challenges (EICs). Of the 38 FFPE specimen challenges, 36 (95%) met the 80% grading consensus threshold. Two of 38 (5%) challenges failed to meet the 80% grading threshold, both involving break-apart probes. Fourteen of 16 (88%) EICs met the 80% “grading” consensus threshold, while 2 (12%) failed, including the misinterpretation of an ALK rearrangement in 1 challenge and the incorrect identification of solid tumors associated with MDM2 amplification in the other challenge. A total of 38 brain/glioma FFPE specimen challenges were provided from 2006–2025 (all involving the deletion status of 1p36 and/or 19q13 regions), and 35 (92%) met the 80% grading consensus threshold. Only 3 (8%) challenges failed to meet the 80% grading threshold. Conclusions.— Overall, this data review demonstrates that clinical cytogenomic laboratories are highly skilled at accurately detecting and interpreting genetic abnormalities by FISH in the setting of FFPE solid tumor and brain/glioma specimens.

Background: Anatomic isthmus 3 (AI 3) is defined as the myocardium between the pulmonary valve annulus and the ventricular septal defect patch that persists after tetralogy of Fallot (ToF) repair. Ventricular tachycardia (VT) propagated through slow conducting AI 3 (SCAI 3) represents a significant cause of morbidity in ToF. There is an unmet need for non-invasive identification of SCAI 3 in patients with ToF. Objectives: To assess whether the anatomic features of AI 3 as derived from cardiac computed tomography (CT) can predict slow conduction velocity during EP study. Methods: This retrospective single-center study included patients with ToF who underwent an electrophysiologic study and had AI 3 width measured from the pre-procedure cardiac CT. All patients underwent programmed ventricular stimulation, and electroanatomic. Logistic regression was performed to assess the relationship between AI 3 width and the presence of SCAI 3. Results: Of 27 consecutive patients with ToF, twelve patients were found to have SCAI 3, and ten patients were found to have SCAI 3 mediated VT. The AI 3 was significantly narrower in patients with SCAI 3 compared to those with normal AI 3 conduction (18.4 +/- 6.6 mm vs. 29.2 +/- 9.0 mm; p = 0.001). An AI 3 width above 21.5 mm carried a negative predictive value of 80.0%. Conclusion: In adults with repaired ToF referred for electrophysiology study, a narrower CT-derived AI 3 width was associated with SCAI 3 identification. AI 3 width measured on a CT obtained before PV replacement could help guide invasive risk stratification.

Background: Acute kidney injury (AKI) is a common complication of COVID-19-associated acute respiratory distress syndrome (ARDS), yet the impact of extracorporeal membrane oxygenation (ECMO) on outcomes in this high-risk population remains unclear. Methods: We performed a retrospective, survey-weighted study using the National Inpatient Sample (NIS) database from 2020–2022 to compare outcomes among adults hospitalized with COVID-19-associated ARDS and AKI managed with invasive mechanical ventilation (IMV) alone versus IMV and ECMO. The primary outcome was in-hospital mortality, while secondary outcomes included renal replacement therapy (RRT), complications, hospital length of stay (LOS), and healthcare utilization. Results: Among 198,395 hospitalizations with COVID-19 ARDS complicated by AKI, 4730 received IMV and ECMO. ECMO use was not associated with statistically significantly lower adjusted in-hospital mortality (adjusted odds ratio [aOR] 0.96, 95% CI 0.81–1.12). However, ECMO was associated with greater odds of RRT, intracranial hemorrhage, disseminated intravascular coagulation, cardiogenic shock, vasopressor use, tracheostomy, acute liver failure, deep vein thrombosis, ischemic stroke and ICU-acquired weakness. ECMO was also associated with longer LOS and higher hospitalization charges. Conclusions: Among hospitalizations with COVID-19-associated ARDS and AKI, ECMO was not associated with statistically significantly lower adjusted in-hospital mortality but was associated with markedly higher complication burden, longer hospitalization, and substantially greater healthcare resource utilization.

Abstract Background Spinal cord stimulation (SCS) is an important modality for treating chronic pain in patients who have failed conservative therapy and a substantial portion of the population rely on fee-for-service Medicare or Medicaid for coverage. We aimed to determine physician professional fee reimbursement rates and the ratio of Medicaid to Medicare professional fee reimbursement (MMI) for three common Current Procedural Terminology (CPT) codes related to SCS therapy (63650, 63685, and 63655) across states. Secondarily, we explored trends in utilization and reimbursement of these procedures by Medicare at the national level between 2013 and 2023. Methods Medicaid professional fee reimbursement data were extracted from publicly available fee schedules where available for individual states, while Medicare reimbursement data were extracted from the Centers for Medicare and Medicaid Services (CMS) Physician Fee Schedule. Baseline and wage-adjusted MMI values were calculated for each state. Results Medicaid reimbursed 11.5–21.0% less than Medicare across the evaluated CPT codes after wage adjustment, with differences of 11.8% for CPT 63650 (facility), 18.0% for CPT 63650 (non-facility), 11.5% for CPT 63685 (facility), and 21.0% for CPT 63655 (facility). Medicaid MMI values ranged from 0.397–1.87 across codes and settings. State-level Medicaid professional fee reimbursement varied substantially, ranging from $194.52–$639.38 for CPT 63650 (facility), $978.72–$2,781.65 for CPT 63650 (non-facility), $160.82–$558.00 for CPT 63685 (facility), and $375.97–$1,045.15 for CPT 63655 (facility); Medicare reimbursement was substantially less variable. From 2013–2023, Medicare utilization, rendering providers, beneficiaries, and standardized payments generally increased, although trends varied by CPT code and site of service. Conclusions Medicare physician professional fee reimbursement largely exceeds Medicaid physician professional fee reimbursement for three of the most common SCS procedural codes, suggesting potential access barriers to chronic pain procedures. Medicaid reimbursement shows considerable variation across states and among procedural codes, suggesting substantial interstate heterogeneity in Medicaid rate-setting that may reflect differences in state policy priorities or other factors not analyzed in this study.

BACKGROUND: The impact of life-course blood pressure (BP) trajectories on later-life focal left ventricular (LV) fibrosis by late gadolinium enhancement (LGE) remains elusive. METHODS: MyoFit46 prospectively recruited ≈500 participants from a 1946 birth cohort for a cardiovascular magnetic resonance scan at 77 years, assessing LV LGE calculated using the 3-SD method or 5-SD method. Systolic BP (SBP) and diastolic BP were recorded at 36, 43, 53, 63, 69, and 77 years. For each participant, annual rates of BP change (steepness) and area under the BP trajectory (cumulative burden) for each age interval were calculated using mixed-effects models. Associations between life-course BPs and LGE were tested using generalized linear models, adjusted for antihypertensives, demographics, lifestyle, and comorbidities. Time-to-event associations between LGE and incident major adverse cardiovascular event (hospitalizations for coronary artery disease, stroke, heart failure, and atrial/ventricular arrhythmias; n=29) were also evaluated. RESULTS: Among 472 participants (54% male), each 10 mm Hg greater individual SBPs at 36 to 69 years were associated with 6% to 11% greater LV LGE calculated using the 3-SD method (all P ≤0.033), whereas each 10 mm Hg sustained greater SBPs on any age interval from 36 to 69 associated with 16% to 24% greater LGE calculated using the 3-SD method at 77(all P ≤0.005), independent of SBP at 77 years. Each 1 mm Hg/y steeper SBP rise during age intervals 36 to 43, 43 to 53, and 53 to 63 was associated with 6% to 12% greater LGE calculated using the 3-SD method at 77 years. LGE presence was associated with greater major adverse cardiovascular event rates (hazard ratio, 2.5 [95% CI, 1.2–5.2]). CONCLUSIONS: Higher life-course BPs, cumulative burden, and steeper increases were associated with greater older-age LV LGE, which was linked to incident major adverse cardiovascular events. BP trajectories, beyond single-point BP measurements, warrant further investigation as tools to guide BP management strategies.

Background: Subtotal colectomy (STC) with end ileostomy (EI) is usually the first surgical stage for patients with ulcerative colitis (UC) who fail medical treatment, most often with biological agents. Is there a difference in surgical outcome after failure of one or two biologicals vs. three or four? Methods: A retrospective study of all patients who underwent STC with EI for UC (5-2018 to 1-2022). After excluding emergent cases, the elective cohort was divided into patients who failed 1–2 biologicals (group 1–2) vs. patients who failed 3–4 biologicals (group 3–4), and surgical outcomes were compared. Data collected included patients’ demographics, preoperative clinical manifestations, and operative and postoperative outcomes. Results: Ninety-eight patients underwent STC for UC, and of them, 53 were elective. Thirty patients failed 1–2 biologics (group 1–2), and 23 failed 3–4 biologics (group 3–4). The groups were similar in average age (37.6 ± 11 vs. 32.7 ± 10), BMI (26.7 ± 6 vs. 27.7 ± 7), number of years with UC (9.5 ± 9 vs. 9 ± 8), rate of steroid dependence (20 (67%) vs. 13 (57%)) but differed in sex; there were 25 (83%) males in group 1–2, and 8 (35%) in group 3–4 (p < 0.01). The operative approaches were similar, as was the operative time (217 ± 74 vs. 210 ± 79 min). The length of hospital stay was 3.2 ± 1 days for group 1–2 and 5 ± 6 days for group 3–4 (p = 0.14). Postoperative complications were seen in 10 patients (33%) vs. 7 patients (30%) (p = 0.82), and of them, two (7%) and two (9%) (p = 0.82) had Venous thromboembolism (VTE), respectively. Only 20 patients (67%) in group 1–2 and 16 patients (70%) in group 3–4 (p = 0.82) progressed to a second stage of an Ileoanal pouch (IPAA) at 11.1 ± 4 and 9.2 ± 2 months, respectively. The overall average follow-up time was 41.1 months. Conclusions: Ulcerative Colitis patients who fail 3–4 biological agents and choose to go to elective STC with EI have very similar surgical outcomes compared to patients who choose elective surgery after failing only 1–2 biological agents in the same time span of known disease. UC patients with severe colitis and poor quality of life who fail two lines of biological agents may be better off electing surgical treatment than failing more biologics and then going to surgery. On the other hand, patients who try 3–4 biologics may expect no worse surgical outcomes than after 1–2 biologics.

Chronic liver disease represents a substantial global health burden, yet effective anti-fibrotic therapies remain elusive, largely due to an incomplete understanding of extracellular matrix (ECM) remodeling. While historical research prioritized the role of matrix metalloproteinase (MMP) deficiency in fibrogenesis, clinical outcomes indicate that broad-spectrum MMP modulation is paradoxically ineffective. This review synthesizes current evidence to demonstrate that hepatic fibrosis is driven by a complex regulatory imbalance wherein tissue inhibitors of metalloproteinases (TIMPs) sustain a pathological microenvironment. We highlight that TIMPs facilitate fibrogenesis through two primary mechanisms: the inhibition of MMP-mediated ECM degradation and the suppression of apoptosis in activated hepatic stellate cells (HSCs), a process exacerbated by mechanotransduction-driven feedback loops. Importantly, we address the functional redundancy within the TIMP family, as evidenced by the progression of fibrosis in TIMP-1-deficient models, which challenges traditional linear regulatory paradigms. Ultimately, we propose that the future of fibrosis treatment necessitates a shift from broad-spectrum enzyme modulation toward precision molecular strategies, including small-molecule inhibition, antisense oligonucleotides, and epigenetic reprogramming aimed at restoring the physiological MMP/TIMP equilibrium within the fibrotic niche.

Background: We report a case to demonstrate that targeted eosinophil depletion with Benralizumab (anti-IL-5 receptor α therapy) can induce the complete functional and structural reversal of advanced EGPA-associated cardiomyopathy. Case Presentation: A 56-year-old woman with a decade-long history of EGPA presented with progressive nonischemic dilated cardiomyopathy and a nadir ejection fraction of 25–30%. Cardiac MRI demonstrated diffuse nonischemic late gadolinium enhancement consistent with eosinophil-mediated myocardial injury. Despite the optimization of guideline-directed medical therapy, complete recovery was not achieved until benralizumab was initiated. Following biologic therapy, the ejection fraction recovered to 50% and severe mitral regurgitation regressed to mild. The exercise capacity was preserved throughout, with a peak VO2 of 117% and 111% of predicted before and after biologic therapy, respectively. The patient remains in NYHA Class I at the one-year follow-up. Discussion: We describe a case with EGPA-associated non-ischemic cardiomyopathy treated with benralizumab achieving the complete recovery of ventricular function and achieving the complete independence of steroid therapy. Conclusions: This case emphasizes the importance of identifying the inflammatory etiology of cardiomyopathy, optimizing GDMT systematically, and considering targeted biologic therapy directed at the underlying disease.

Abstract Accurate left ventricular (LV) segmentation and ejection fraction (EF) estimation from echocardiographic videos are important for cardiovascular risk stratification, but automated methods remain sensitive to domain shift and limited site-specific annotations. We present EchoMed Agent, an imaging-driven framework that integrates MedSAM2, a video segmentation foundation model adapted using rank-4 low-rank adaptation in the mask-decoder attention layers, with a constrained GPT-5.2–based natural-language tool-routing interface for prompt-guided LV segmentation and automated functional assessment. A lightweight axis-regression module, AxisHead, applies mask-guided pooling to frozen vision-transformer features to predict the LV long axis for single-plane area-length volume and EF estimation. The framework was initially trained on EchoNet-Dynamic and subsequently evaluated using few-shot adaptation on an independent Mayo Clinic cohort of 98 studies. With 20 labeled site-specific studies, EchoMed Agent achieved a Dice coefficient of 0.940 and a median absolute EF error of 4.33 percentage points on the Mayo cohort. This Dice score exceeded the 0.932 obtained by an EchoNet-Dynamic–trained MedSAM2 model transferred to Mayo without site-specific adaptation. Overall, 83.3% of evaluated cases had an absolute EF error of no more than 10 percentage points. These findings suggest that parameter-efficient site-specific adaptation can reduce the number of required annotations while maintaining clinically relevant segmentation and EF-estimation accuracy on an independent institutional cohort.