Florida Hospital Medical Group

Checkpoint inhibitor pneumonitis (CIP) is a serious immune-related adverse event. Patients with interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD) may be at increased risk, but data comparing these populations is limited. We aimed to evaluate differences in CIP incidence, onset, recurrence, and outcomes among patients with ILD, COPD, and those without pre-existing lung disease. We conducted a retrospective cohort study using the TriNetX Research Network, identifying patients who received immune checkpoint inhibitors (ICIs) between January 2017 and January 2023. Patients were stratified into ILD, COPD, and control groups. CIP was identified using ICD codes. Propensity score matching (1:1:1) was used to adjust for baseline characteristics. Outcomes included CIP incidence, time to onset, recurrence, hospitalisation, and mortality. Among 184,000+ ICI recipients, 3147 had ILD, 8657 had COPD, and 47,031 had no known lung disease. After matching (n = 3147/group), CIP incidence was highest in ILD patients (4.6%) compared to COPD (1.9%) and controls (1.5%) (p < 0.001). Time to CIP onset was similar across groups. ILD patients with CIP had higher recurrence (16.4% vs. 9.1% and 8.3%) and higher all-cause hospitalisation (61% vs. 40% and 39%) compared to COPD and control groups. All-cause mortality was also higher in the ILD-CIP group (41.1%). ILD significantly increases the risk of developing CIP and worsens associated outcomes, including recurrence and mortality. These findings support closer surveillance and risk stratification in ICI-treated patients with underlying ILD.

Background Cutaneous squamous cell carcinoma (cSCC) causes more annual mortality than metastatic melanoma. However, risk stratification protocols remain based solely on clinicopathologic features, excluding tumor biology. (Table 1) Objective To illustrate how integration of 40-gene expression profile (GEP) testing influences prognostic assessment and post-treatment management in high-risk cSCC. Methods We present a case report of a 70-year-old male whose incidental cSCC was reclassified as high-risk following 40-GEP testing despite histologic clearance, resulting in enhanced surveillance. Results Tumor profiling yielded a Class 2A (higher risk) result, which altered post-operative follow-up strategies beyond conventional staging. Conclusion Gene expression profiling provides valuable, individualized prognostic data, which may improve management of high-risk cSCC patients and should be considered for broader integration into clinical guidelines.

Pathogenic variants in GABAA receptor subunit genes (GABR*) are important contributors to rare and common genetic epilepsies. Here, we present a comprehensive analysis of variants in GABRB1, which encodes the GABAA receptor β1 subunit, by revealing their functional implications, establishing genotype-phenotype correlations and evaluating treatment response. Clinical information on individuals carrying a GABRB1 variant was obtained through an international collaboration and literature review. Our cohort included 19 individuals (7 males, 12 females) from 15 families harbouring 13 different GABRB1 variants (11 missense, 1 indel, 1 stop). Functional analysis was performed using two-electrode voltage-clamp recordings in Xenopus laevis oocytes. For all 11 missense variants, α1β1γ2 GABAA receptors with a single mutant β1 subunit were used. Four missense variants were selected for further functional analysis using α5β1γ2 GABAA receptors with two mutant β1 subunits. Gain-of-function (GoF) effects, characterized by increased GABA-sensitivity, were observed for eight missense variants. Loss-of-function (LoF) effects were observed for one variant and no functional effects for two variants. Clinically, GoF variants were only observed in individuals with severe early-onset disease, including profound intellectual disability, hypotonia and early mortality. Additionally, cortical visual impairment, dysmorphisms and cortical atrophy were exclusive to this cohort. By integrating previously reported clinical data for variants in other GABR* genes, we validated that these features were associated with GoF variants more broadly. The only LoF variant was identified in a nuclear family with the relatively milder syndrome of genetic epilepsy with febrile seizures plus. Seizures were therapy-resistant in all individuals with GoF variants and a single individual with a LoF variant. The GABAergic anti-seizure medication (ASM) vigabatrin caused life-threatening side-effects in two individuals with GoF variants, while the sodium-channel blocker (SCB) lamotrigine exacerbated seizures in a single individual carrying a LoF variant. By integrating data from literature on all GABR* variants, we observed a potential dichotomy in treatment responses: GABAergic and broad-spectrum ASMs, such as valproate and levetiracetam, were more effective for individuals with LoF variants in GABR* genes, while SCBs showed greater benefit for GoF variants. Additionally, there is an increased risk of adverse effects of SCBs in LoF and vigabatrin in GoF variants. Our results highlight the importance of functional characterization of variants and clinical predictors in guiding treatment strategies for individuals with GABRB1 and other GABR* variants, although larger prospective studies are needed to confirm these observations.

This study aims to provide a comprehensive review of contemporary approaches to estimating the residual value of rebuilt vehicles in the U.S. dealer market. The relevance of this work is driven by the scale and dynamics of the auction segment for rebuilt and salvage vehicles, whose revenue rivals that of the midsize new-car market, and whose online segment is projected to grow at a compound annual rate of 13.7% through 2030. The novelty of the research lies in bringing together various types of data. This data comes from VIN parsing, operational logs from Copart, IAA, OpenLane, telematics streams coming from Geotab, and high-precision visual checks. It has been observed that the shift from expert visual appraisal to digital valuation methods has significantly reduced the mean absolute error in RV forecasts, while also shortening the days-to-sale and decreasing cosmetic damage arbitration rates. UVeye, Mitchell+PAVE, and Ravin AI systems will incorporate models with visual features, while conformal quantile regression will ensure guaranteed coverage, enabling automatic adjustments to financial terms. However, new risks have emerged: the increase in deepfake manipulations of photographic content, alongside regulatory requirements (SB-362), will impose very stringent demands on verification as well as the protection of personal and telematics data. This article will be of use to analysts, dealers, AI solution developers, and researchers in the fields of residual value estimation and risk management in the used-vehicle market.

No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors. Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service. From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses leading to ERCP were chronic (47.2%) and acute pancreatitis (43.2%); biliary diagnoses were calculus (68.3%) and obstruction (14.8%). No ERCP was available for 25.0% of pancreatic encounters and 8.1% of biliary encounters. In multivariable analysis, children with public insurance, rural residence, or of Black race were less likely to have pancreatic ERCP availability; those with rural residence or Asian race were less likely to have biliary ERCP availability. Black children or those with public insurance were less likely to undergo pancreatic ERCP where available. Among encounters for calculus or obstruction, those of Black race or admitted to hospitals in the West were less likely to undergo ERCP when available. One-in-four children with pancreatic disorders and one-in-12 with biliary disorders may have limited access to ERCP. We identified racial and geographic disparities in availability and utilization of ERCP. Further studies are needed to understand these differences to ensure equitable care.

697 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance (AVE 1LM) + best supportive care (BSC) improved overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients (pts) with locally advanced/metastatic urothelial carcinoma (la/mUC) with no disease progression following 4-6 cycles of platinum-based chemotherapy (PBC). PATRIOT-II aimed to describe real-world outcomes in pts with la/mUC treated with AVE 1LM who were progression-free after 1L PBC. We hypothesized that outcomes would be similar to those of JAVELIN Bladder 100. Methods: PATRIOT-II is an observational, retrospective study in US pts with la/mUC treated in geographically dispersed community and academic centers. Pts receiving AVE 1LM were eligible. Data were collected via medical records for a minimum of 52 weeks (wks) from AVE 1LM initiation. This analysis focuses on ≥24 wks post AVE 1LM initiation. Survival and safety outcomes were assessed; analyses are descriptive in nature. Results: 160 pts from 37 sites, a mix of oncology practices and community/academic centers, were included with median age, 70 (range, 40-90) years; 123 (77%) male; 118 (74%) White, non-Hispanic; 77 (49%) lower tract and 49 (31%) upper tract tumors; 119 (74%) ECOG PS 0/1; 70 (44%) and 51 (32%) known visceral (excluding bone) or non-visceral metastases (mets), respectively; 31 (19%) liver mets; and 64 (40%) creatinine clearance &gt;60 mL/min. 100 (62.5%) and 60 (37.5%) pts had received 1L cisplatin or carboplatin, respectively. 130 pts (objective response rate, 81% [complete response, 21; partial response, 109]) had an investigator-assessed response to 1L PBC. Pts initiated AVE 1LM at a median of 4 wks (IQR, 3-6) after PBC completion. At data cutoff, 120 pts (75%) had discontinued AVE 1LM, 89 (74% of 120) due to progression/adverse events (AEs)/other non-death related reasons. Median time on AVE 1LM was 4.1 months (mo) (IQR, 2.3-8.7); median follow-up time post AVE 1LM initiation was 11.5 mo (IQR, 7.5-16.3). Table shows OS and PFS data. Most common documented treatment-related AEs (any grade) included hypothyroidism (n=7 [4%]), anemia (n=6 [4%]), blood creatinine increased (n=6 [4%]), fatigue (n=6 [4%]), and nausea (n=6 [4%]). Grade 3+ AEs occurred in 19 (12%), with no Grade 5 AEs. No new safety signals were noted. Conclusions: Results complement JAVELIN Bladder 100 and align with other AVE 1LM real-world studies. Limitations include retrospective data, lack of randomization and central scan review, missing data, selection bias, and confounders. PATRIOT-II further supports the level I evidence for AVE 1LM as standard of care in la/mUC not progressing on 1L PBC. [Table: see text]

In this study, the authors describe their 10-year single-institution experience with single-step complete corpus callosotomy (CCC) for seizure management in pediatric and adult patients with catastrophic, medically refractory, nonlocalizing epilepsy at Advent Health Orlando. The authors conducted a retrospective observational study of patients aged 6 months to 49 years who underwent clinically indicated CCC for drug-resistant nonlocalizing epilepsy at Advent Health Orlando between July 2011 and July 2021. Follow-up ranged from 12 months to 10 years. Of the 101 patients (57% of whom were male) who met eligibility criteria, 81 were pediatric patients and 20 were ≥ 18 years. All patients had seizures that appeared poorly lateralized on both electroencephalograms and clinical semiological studies. Of 54 patients with drop seizures before CCC, 29 (54%) achieved stable freedom from drop seizures after CCC. Of the 101 patients, 14 (13.9%) experienced stable resolution of all types of clinical seizures (International League Against Epilepsy classes 1 and 2). The most common postoperative neurological complication was a transient disconnection syndrome, observed in 50% of patients; of those patients, 73% experienced syndrome resolution within 2 months after surgery, and all resolved by the 2-year follow-up. Formal neuropsychological test results were stable in 13 patients assessed after CCC. CCC is an effective and well-tolerated palliative surgical technique. In this study, drop attacks were reduced after CCC but could recur for the first time as late as 44 months after surgery. Other seizure types were also reduced postoperatively but could recur for the first time as late as 28 months after surgery. Nearly 14% of patients achieved stable and complete freedom from seizures after CCC. Re-evaluation after CCC can reveal lateralized seizure onset in some patients.

Mutations in the gene encoding syntaxin binding protein 1 (STXBP1) have been implicated in a wide variety of epileptic encephalopathies. Although the recognized phenotypes of patients with STXBP1 encephalopathies have broadened in recent years, no case of reflex seizures, particularly musicogenic seizures, has been reported in the literature. We present an 18-year-old woman with STXBP1 encephalopathy and seizures that are stereotypically reproducible in response to a variety of audible stimuli. An 18-year-old woman with a history of profound intellectual disability, confirmed STXBP1 genetic defect via genetic testing, and seizures beginning as infantile spasms during childhood, who presented to the epilepsy monitoring unit for seizure characterization. Her mother reported reproducible seizures triggered by a particular cell phone ringtone, music from a certain automobile television commercial and certain beeping alarm sounds. In response, the patient had clinically stereotyped seizures associated with staring, behavioral arrest, followed by eye deviation to the left, tonic stiffening in upper and lower extremities and labored breathing, lasting between 30 seconds and 2 minutes. These seizures were reliably reproducible within a few seconds of exposure to the auditory stimulus. During hospitalization, mother played one of the cell phone ringtones known to trigger seizures for the patient, which resulted in induction of a seizure characterized by diffuse electrodecrement, subsequent emergence of frontal-predominant theta which was followed by progressive diffuse attenuation and semi-rhythmic slowing over the right posterior quadrant. This is the first case to describe musicogenic or other reflex seizures in a patient with STXBP1 encephalopathy.