Procedural Volume and Outcomes with Atrial Fibrillation Ablation: A Report from the NCDR AFib Ablation Registry.

BACKGROUND: The association between hospital and physician procedure volume outcome has not been well evaluated for atrial fibrillation (AF) ablation in contemporary practice. OBJECTIVE: To determine the association between hospital and physician AF ablation volume and procedural success (isolation of all pulmonary veins) and major adverse events (MAE). METHODS: Procedures reported to the NCDR AFib Ablation Registry between July 2019 and June 2022 were included. Hospital and physician procedural volumes were annualized and stratified into quartiles (Q) to compare outcomes. Three level hierarchical (patient, hospital and physician) models were used to assess the procedural volume outcome relationship. RESULTS: A total of 70,296 first-time AF ablations at 186 U.S. hospitals were included. Overall, procedural success and MAE rate were 98.5 % and 1.0% respectively. With hospital volume (Q4) as a reference, the likelihood of procedural success was lower for Q1 (OR 0.44, 95%CI 0.29-0.68), Q2 (OR 0.50, 95%CI 0.33-0.75) and Q3 (OR 0.60, 95%CI 0.40-0.89); the results were similarly signifant for physician volume. With MAE for hospitals, there was an inverse procedural volume relationship for Q1 (OR 1.78, 95%CI 1.26-2.51) but not for Q2 (OR 1.06, 95%CI 0.77-1.46) or Q3 (OR 1.19, 95%CI 0.89-1.58) and similarly for physicians in Q1 and Q2, not in Q3. An adjusted MAE ≤ 1% was predicted by an annual volume of approximately 190 for hospitals and 60 for physicians. CONCLUSION: In this national cohort, hospital and physician AF ablation procedural volumes were directly related to acute procedural success and inversely related to rates of MAE.

Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A.

PURPOSE: National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring EGFR mutations. METHODS: Patients with advanced pretreated cancers other than lung cancer found to have selected actionable EGFR mutations were offered participation in Arm A. Previous therapy with an EGFR TKI was not allowed. Patients received afatinib 40 mg once daily continuously until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival (OS). RESULTS: Seventeen patients received protocol therapy. Tumor types included glioblastoma multiforme (GBM) (13), gliosarcoma (1), adenocarcinoma not otherwise specified (NOS) (2), and adenosquamous carcinoma of the breast (1). Fifty-nine percent of patients received ≥2 lines of previous therapy. The ORR was 11.8% (90% CI, 2.1 to 32.6), with one complete response lasting 16.4 months (GBM harboring a rare exon 18 EGFR-SEPT14 fusion) and one partial response lasting 12.8 months (adenocarcinoma NOS with the classic EGFR mutation, p.Glu746_Ala750del). Three patients had stable disease. The 6-month PFS was 15% (90% CI, 0 to 30.7); the median OS was 9 months (90% CI, 4.6 to 14.0). Rash and diarrhea were the most common toxicities. CONCLUSION: Afatinib had modest activity in a cohort of patients with heavily pretreated cancer with advanced nonlung, EGFR-mutated tumors, but the trial's primary end point was not met. Further evaluation of afatinib in GBM with EGFR exon 18 fusions may be of interest.

The effect of high-dose erythropoietin perinatally on retinal function in school-aged children born extremely or very preterm.

PURPOSE: To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm. DESIGN: Randomized, double-blind clinical trial follow-up plus cohort study. METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. STUDY POPULATION: extremely or very preterm-born children aged 7-15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period. INCLUSION CRITERIA: participation in an ongoing neuropediatric study (EpoKids), written informed consent (IC). EXCLUSION CRITERIA: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited. INCLUSION CRITERIA: term birth, IC. EXCLUSION CRITERIA: any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses. OBSERVATION PROCEDURES: Electroretinography (ERG) was performed with the RETeval device (LKC Technologies, Inc., Gaithersburg MD). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group. MAIN OUTCOME MEASURES: Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only). RESULTS: No differences in ERG parameters between EPO (n=52; 104 eyes) and placebo (n=35; 70 eyes) subgroups were observed (all corrected p>0.05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n=52; 104 eyes) subgroup (coefficient/95% confidence interval (CI) = 0.53/0.21 to 0.85 and 0.36/0.13 to 0.60; p = 0.012 and 0.022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% CI = -4.33/-6.88 to -1.78; p = 0.011). Secondary outcomes were comparable across subgroups. CONCLUSIONS: Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.

Genetic modifiers of somatic expansion and clinical phenotypes in Huntington's disease reveal shared and tissue-specific effects.

Huntington's disease (HD), due to expansion of a CAG repeat in HTT , is representative of a growing number of disorders involving somatically unstable short tandem repeats. We find that overlapping and distinct genetic modifiers of clinical landmarks and somatic expansion in blood DNA reveal an underlying complexity and cell-type specificity to the mismatch repair-related processes that influence disease timing. Differential capture of non-DNA-repair gene modifiers by multiple measures of cognitive and motor dysfunction argues additionally for cell-type specificity of pathogenic processes. Beyond trans modifiers, differential effects are also illustrated at HTT by a 5'-UTR variant that promotes somatic expansion in blood without influencing clinical HD, while, even after correcting for uninterrupted CAG length, a synonymous sequence change at the end of the CAG repeat dramatically hastens onset of motor signs without increasing somatic expansion. Our findings are directly relevant to therapeutic suppression of somatic expansion in HD and related disorders and provide a route to define the individual neuronal cell types that contribute to different HD clinical phenotypes.

Drinking water source and exposure to regulated water contaminants in the California Teachers Study cohort.

BACKGROUND: Pollutants including metals/metalloids, nitrate, disinfection byproducts, and volatile organic compounds contaminate federally regulated community water systems (CWS) and unregulated domestic wells across the United States. Exposures and associated health effects, particularly at levels below regulatory limits, are understudied. OBJECTIVE: We described drinking water sources and exposures for the California Teachers Study (CTS), a prospective cohort of female California teachers and administrators. METHODS: Participants' geocoded addresses at enrollment (1995-1996) were linked to CWS service area boundaries and monitoring data (N = 115,206, 92%); we computed average (1990-2015) concentrations of arsenic, uranium, nitrate, gross alpha (GA), five haloacetic acids (HAA5), total trihalomethanes (TTHM), trichloroethylene (TCE), and tetrachloroethylene (PCE). We used generalized linear regression to estimate geometric mean ratios of CWS exposures across demographic subgroups and neighborhood characteristics. Self-reported drinking water source and consumption at follow-up (2017-2019) were also described. RESULTS: Medians (interquartile ranges) of average concentrations of all contaminants were below regulatory limits: arsenic: 1.03 (0.54,1.71) µg/L, uranium: 3.48 (1.01,6.18) µg/L, GA: 2.21 (1.32,3.67) pCi/L, nitrate: 0.54 (0.20,1.97) mg/L, HAA5: 8.67 (2.98,14.70) µg/L, and TTHM: 12.86 (4.58,21.95) µg/L. Among those who lived within a CWS boundary and self-reported drinking water information (2017-2019), approximately 74% self-reported their water source as municipal, 15% bottled, 2% private well, 4% other, and 5% did not know/missing. Spatially linked water source was largely consistent with self-reported source at follow-up (2017-2019). Relative to non-Hispanic white participants, average arsenic, uranium, GA, and nitrate concentrations were higher for Black, Hispanic and Native American participants. Relative to participants living in census block groups in the lowest socioeconomic status (SES) quartile, participants in higher SES quartiles had lower arsenic/uranium/GA/nitrate, and higher HAA5/TTHM. Non-metropolitan participants had higher arsenic/uranium/nitrate, and metropolitan participants had higher HAA5/TTHM. IMPACT: Though average water contaminant levels were mostly below regulatory limits in this large cohort of California women, we observed heterogeneity in exposures across sociodemographic subgroups and neighborhood characteristics. These data will be used to support future assessments of drinking water exposures and disease risk.

American Society of Transplant Surgeons Normothermic Regional Perfusion Standards: Ethical, Legal, and Operational Conformance.

BACKGROUND: The American Society of Transplant Surgeons convened a multidisciplinary working group to address operational, ethical, and legal considerations surrounding normothermic regional perfusion (NRP) procurement. METHODS: The working group, comprising members from American Society of Transplant Surgeons and AST across various disciplines including transplant surgery, hepatology, critical care, and bioethics, collaborated to formulate recommendations and guidance for NRP procurement. RESULTS: The following topics were identified by the group as essential standards that need to be addressed for ethical, legal, and operational conformance: terminology; conceptualization of death in the context of NRP; and communication, logistics, and training and competency. CONCLUSIONS: Fourteen recommendations that support the ethical and legal acceptability of NRP in the United States and set expectations for the conduct of NRP procedures are provided.

A cortical surface template for human neuroscience.

Neuroimaging data analysis relies on normalization to standard anatomical templates to resolve macroanatomical differences across brains. Existing human cortical surface templates sample locations unevenly because of distortions introduced by inflation of the folded cortex into a standard shape. Here we present the onavg template, which affords uniform sampling of the cortex. We created the onavg template based on openly available high-quality structural scans of 1,031 brains-25 times more than existing cortical templates. We optimized the vertex locations based on cortical anatomy, achieving an even distribution. We observed consistently higher multivariate pattern classification accuracies and representational geometry inter-participant correlations based on onavg than on other templates, and onavg only needs three-quarters as much data to achieve the same performance compared with other templates. The optimized sampling also reduces CPU time across algorithms by 1.3-22.4% due to less variation in the number of vertices in each searchlight.

Serratus anterior plane block improves pain and incentive spirometry volumes in trauma patients with multiple rib fractures: a prospective cohort study.

Background: Rib fractures are common injuries associated with considerable morbidity, long-term disability, and mortality. Early, adequate analgesia is important to mitigate complications such as pneumonia and respiratory failure. Regional anesthesia has been proposed for rib fracture pain control due to its superior side effect profile compared with systemic analgesia. Our objective was to evaluate the effect of emergency physician-performed, ultrasound-guided serratus anterior plane block (SAPB) on pain and respiratory function in emergency department patients with multiple acute rib fractures. Methods: This was a prospective observational cohort study of adult patients at a level 1 trauma center who had two or more acute unilateral rib fractures. Eligible patients received a SAPB if an emergency physician trained in the procedure was available at the time of diagnosis. Primary outcomes were the absolute change in pain scores and percent change in expected incentive spirometry volumes from baseline to 3 hours after rib fracture diagnosis. Results: 38 patients met eligibility criteria, 15 received the SAPB and 23 did not. The SAPB group had a greater decrease in pain scores at 3 hours (-3.7 vs. -0.9; p=0.003) compared with the non-SAPB group. The SAPB group also had an 11% (CI 1.5% to 17%) increase in percent expected spirometry volumes at 3 hours which was significantly better than the non-SAPB group, which had a -3% (CI -9.1% to 2.7%) decrease (p=0.008). Conclusion: Patients with rib fractures who received SAPB as part of a multimodal pain control strategy had a greater improvement in pain and respiratory function compared with those who did not. Larger trials are indicated to assess the generalizability of these initial findings.

The effect of perinatal high-dose erythropoietin on retinal structural and vascular characteristics in children born preterm.

PURPOSE: To study the long-term effects of perinatal high-dose recombinant human erythropoietin (rhEPO) on macular structural and vascular development in preterm children. DESIGN: Randomized, double-blind clinical trial follow-up plus cohort study. METHODS: Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. STUDY POPULATION: extremely or very preterm born children aged 7-15 years from an ongoing neuropediatric study (EpoKids). These had been previously randomized to receive either high-dose rhEPO or placebo perinatally. INCLUSION CRITERIA: participation in the EpoKids Study, written informed consent (IC). EXCLUSION CRITERIA: previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Term-born children of comparable age were enrolled as a healthy control (HC) group. INCLUSION CRITERIA: term birth, IC. EXCLUSION CRITERIA: any ocular or visual abnormality, high refractive error. Examiners were blinded regarding intervention status until completion of all analyses. (Participants/guardians remain blinded). OBSERVATION PROCEDURES: Spectral-domain OCT scans (Heidelberg Spectralis system) and OCTA imaging (Zeiss PlexElite 9000) were obtained. Ophthalmological and orthoptic examinations excluded ocular comorbidities. MAIN OUTCOME MEASURES: OCT (central retinal thickness, CRT; total macular volume, TMV), superficial plexus OCTA (foveal avascular zone, FAZ; vessel density, VD; vessel length density, VLD) parameters and foveal hypoplasia grade according to published criteria. RESULTS: Macular vessel density parameters (VD and VLD) were significantly lower (p =0.015, CI-95: 0.01 to 0.06 and p=0.015, CI-95: 0.74 to 3.64) in the EPO group (n= 52) when compared to placebo (n=35). No other significant differences were observed between the EPO and placebo group. When comparing the intervention subgroups to HC we found six significant differences in OCT and OCTA parameters (FAZ, VD, VLD and CRT comparing HC and EPO group; FAZ and CRT when comparing HC and placebo group). CONCLUSIONS: Early high-dose rhEPO in infants born extremely or very preterm affects macular vessel density parameters compared to placebo. Premature birth (regardless of intervention status) affects retinal structure and vascular development. Our findings on macular vascular development do not contraindicate the administration of early high-dose EPO in preterm infants. For further understanding of the role of EPO on macular development and its clinical significance, future studies are needed.

Procedure Volume and Outcomes With WATCHMAN Left Atrial Appendage Occlusion.

BACKGROUND: Procedure volumes are associated with outcomes for many cardiovascular procedures, leading to guidelines on minimum volume thresholds for certain procedures; however, the volume-outcome relationship with left atrial appendage occlusion is poorly understood. As such, we sought to determine the relationship between hospital and physician volume and WATCHMAN left atrial appendage occlusion procedural success overall and with the new generation WATCHMAN FLX device. METHODS: We performed an analysis of WATCHMAN procedures (January 2019 to October 2021) from the National Cardiovascular Data Registry LAAO Registry. Three-level hierarchical generalized linear models were used to assess the adjusted relationship between procedure volume and procedural success (device released with peridevice leak <5 mm, no in-hospital major adverse events). RESULTS: Among 87 480 patients (76.2±8.0 years; 58.8% men; mean CHA2DS2-VASc score, 4.8±1.5) from 693 hospitals, the procedural success rate was 94.2%. With hospital volume Q4 (greatest volume) as the reference, the likelihood of procedural success was significantly less among Q1 (odds ratio [OR], 0.66 [CI, 0.57-0.77]) and Q2 (OR, 0.78 [CI, 0.69-0.90]) but not Q3 (OR, 0.95 [CI, 0.84-1.07]). With physician volume Q4 (greatest volume) as the reference, the likelihood of procedural success was significantly less among Q1 (OR, 0.72 [CI, 0.63-0.82]), Q2 (OR, 0.79 [CI, 0.71-0.89]), and Q3 (OR, 0.88 [CI, 0.79-0.97]). Among WATCHMAN FLX procedures, there was attenuation of the volume-outcome relationships, with statistically significant but modest absolute differences of only ≈1% across volume quartiles. CONCLUSIONS: In this contemporary national analysis, greater hospital and physician WATCHMAN volumes were associated with increased procedure success. The WATCHMAN FLX transition was associated with increased procedural success and less heterogeneity in outcomes across volume quartiles. These findings indicate the importance of understanding the volume-outcome relationship for individual left atrial appendage occlusion devices.

Analysis of automotive paint layers on plastic substrates using chemical imaging µ-FTIR and O-PTIR microspectroscopy.

Automobile paint chips are a crucial piece of trace evidence for forensic investigators. This is because automotive paints are composed of multiple layers, including the primer, basecoat, and clearcoat, each of which has its own chemical composition that can vary by vehicle make, model, year, and manufacturing plant. Thus, Fourier-transform infrared (FTIR) spectral databases for automobile paint systems have been established to aid law enforcement in, for example, narrowing search parameters for a suspect's vehicle. Recently, car manufacturers have implemented primers on plastic substrates that are much thinner (~5 µm) than those on metal substrates, making it more difficult to manually separate for analyses. Here, we evaluated FTIR microspectroscopy (µ-FTIR) and optical photothermal infrared spectroscopy (O-PTIR) to chemically image cross sections of paint chips without manually separating the layers. For µ-FTIR, transmission and transflection modes provided the highest quality spectra compared to reflection and µ-ATR analyses. Point analysis was preferable to chemical imaging, as peaks were identified in the point (MCT) detector's lower spectral range that was below the imaging (FPA) detector's cutoff, such as those associated with titanium dioxide. Reduced spectral range can lead to a similar issue in O-PTIR analyses depending on instrument configuration. However, its complementary Raman spectra showed strong titanium dioxide peaks, providing an alternate means of identification. Both techniques are likely to become more relevant as they are non-destructive and avoid manual separation of the layers. O-PTIR is particularly well-suited for analysis of the thin primer layer due to its superior spatial resolution.

Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial.

PURPOSE: The National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric MATCH trial assigns patients age 1-21 years with refractory malignancies to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with activating alterations in the mitogen-activated protein kinase pathway were treated with ulixertinib, an extracellular signal-regulated kinase (ERK)1/2 inhibitor. METHODS: As there were no previous pediatric data, ulixertinib was initially tested in a dose escalation cohort to establish the recommended phase II dose (RP2D) before proceeding to the phase II cohort. Ulixertinib was administered at 260 mg/m2/dose orally twice a day (dose level 1 [DL1], n = 15) or 350 mg/m2/dose orally twice a day (DL2, n = 5). The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival (PFS). RESULTS: Twenty patients (median 12 years; range, 5-20) were treated, all evaluable for response. CNS tumors comprised 55% (11/20) of diagnoses, with high-grade glioma and low-grade glioma most common (n = 5 each). All CNS tumors except one harbored BRAF fusions or V600E mutations. Rhabdomyosarcoma (n = 5) was the most frequent non-CNS diagnosis. DL1 was declared the RP2D in the dose escalation cohort after dose-limiting toxicities in Cycle 1 occurred in 1/6 patients at DL1 and 2/5 patients at DL2, including fatigue, anorexia, rash, nausea, vomiting, diarrhea, dehydration, hypoalbuminemia, and hypernatremia. No objective responses were observed. Six-month PFS was 37% (95% CI, 17 to 58). Three patients with BRAF-altered CNS tumors achieved stable disease >6 months. CONCLUSION: Ulixertinib, a novel targeted agent with no previous pediatric data, was successfully evaluated in a national precision medicine basket trial. The pediatric RP2D of ulixertinib is 260 mg/m2/dose orally twice a day. Limited single-agent efficacy was observed in a biomarker-selected cohort of refractory pediatric tumors.

The Inventory of Callous-Unemotional Traits (ICU) self-report version: Factor structure, measurement invariance, and predictive validity in justice-involved male adolescents.

The Inventory of Callous-Unemotional Traits (ICU) is a widely used measure of callous-unemotional (CU) traits that may aid in the assessment of the diagnostic specifier "with limited prosocial emotions," which has been added to diagnostic criteria for conduct disorder. Though there is substantial support for use of the ICU total score, the scale's factor structure has been highly debated. Inconsistencies in past factor analyses may be largely attributed to failure to control for method variance due to item wording (i.e., half of the items being worded in the callous direction and half worded in the prosocial direction). Thus, the present study used a multitrait-multimethod confirmatory factor analytic approach that models both trait and method variance to test the factor structure of the ICU self-report in a clinically relevant, high-risk sample of justice-involved male adolescents (N = 1,216). When comparing the fit of empirical and theoretical models, goodness of fit indices (χ² = 1105.877, df = 190, root-mean-square error of approximation = .063, comparative fit index = .916, Tucker-Lewis index = .878, standardized root-mean-square residual = .051) provided support for a hierarchical four-factor model (i.e., one overarching callous-unemotional factor, four latent trait factors) when accounting for method variance (i.e., covarying positively worded items). This factor structure is consistent with the way the ICU was constructed and with criteria for the limited prosocial emotions specifier. In addition, measurement invariance of this factor structure across age, race, and ethnicity was supported, and the predictive validity of the ICU was supported across these demographic groups in predicting self-reported antisocial behavior and rearrests over a 5-year period following an adolescent's first arrest. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Utility of Recovery Room vs Post-Operative Day 1 Radiographs Following Shoulder Arthroplasty.

Background: Postoperative radiographs may be performed on different timelines after shoulder arthroplasty. Radiographs obtained in the post-operative recovery unit (PACU) are often of poorer quality. The purpose of the current study was to explore and compare the quality of PACU radiographs and radiographs performed in the radiology suite on post-operative Day 1 (POD1), as well as determine their impact on changes in post-operative management. Methods: Our series included 50 consecutive anatomic total shoulder arthroplasties (TSA) for which post-operative radiographs were obtained in the PACU and 50 consecutive TSA for which post-operative radiographs were obtained in the radiology suite on POD 1. TSA radiographs were blinded and reviewed by 3 authors and graded on their quality using criteria described using previously published methods. The weighted kappa was used to describe the intra-rater agreement and inter-rater agreement between two raters. Results: There was no difference in age, sex, BMI, and comorbidities between cohorts. Intra-observer reliability was moderate to substantial with weighted kappa values of 0.65±0.07 (p<0.001), 0.58±0.09 (p<0.001), and 0.67±0.07 (p<0.001). Inter-observer reliability was moderate to substantial with weighted kappa values of 0.605±0.07 (p<0.001), 0.66±0.07 (p<0.001), and 0.65±0.08 (p<0.001). When assessing quality of radiographs, 30% of radiographs obtained in PACU were deemed quality while 57% of radiographs obtained in the radiology suite were deemed quality (p<0.001). Conclusion: Post-operative radiographs in the PACU do not alter patient management and are often inadequate to serve as baseline radiographs. Conversely, radiographs obtained in the radiology suite are of higher quality and can serve as a superior baseline radiograph. Level of Evidence: IV.

Phase II study of vemurafenib in children and young adults with tumors harboring BRAF V600 mutations: NCI-COG pediatric MATCH trial (APEC1621) Arm G.

BACKGROUND: This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations. METHODS: Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib. RESULTS: Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to exclusions of low-grade glioma (nâ=â7) and prior BRAF inhibitor therapy (nâ=â7). Enrolled diagnoses were one each of histiocytosis, ameloblastoma, Ewing sarcoma, and high-grade glioma, all with BRAF V600E mutations. Treatment was overall tolerable with mostly expected grade 1/2 adverse events (AE). Grade 3 or 4 AE on treatment were acute kidney injury, hyperglycemia, and maculopapular rash. One patient came off therapy due to AE. One patient (glioma) had an objective partial response and remained on protocol therapy for 15 cycles. CONCLUSION: There was a low accrual rate on this MATCH subprotocol, with only 18% of those who matched with BRAFV600 mutations enrolling, resulting in early termination, and limiting study results (ClinicalTrials.gov Identifier: NCT03220035).

Ectopic sulcular pain: detection and treatment.

Patients who present with acute or chronic posterior dental pain but cannot identify the tooth from which the pain originates may suffer from a common but often unrecognized condition. The present article introduces a new term for this disorder, ectopic sulcular pain (ESP), derived from its unusual presentation, location, and defining symptom. It is tempting to call ESP an infection, but this has not been confirmed. In ESP, oral examination reveals no visual abnormalities, and there are no evident fractures, caries, periodontitis, attachment loss, traumatic occlusion, or periapical abscesses. This confusing symptomatology often leads to incorrect diagnosis and, consequently, treatment that fails to relieve the patient's pain. This article discusses ESP and reports 13 cases in which the condition was identified via intraligamental or topical application of an anesthetic agent to numb the gingiva. In 12 patients, ESP was successfully treated with meticulous oral hygiene, chlorhexidine rinses, and, in some cases, oral antibiotics.

Flicker electroretinogram in preterm infants.

BACKGROUND: Infants born prematurely are at risk of developing retinopathy of prematurity, which is associated with abnormalities in retinal function as measured using electroretinography. The aim of this study was to record non-invasive flicker electroretinograms (ERGs) in preterm infants and compare function of moderate and very or extremely preterm infants. METHODS: In this non-randomized, cross-sectional study, 40 moderate preterm (gestational age (GA) 34 0/7 to 36 6/7 weeks, Group A) and 40 very or extremely preterm infants (GA ≤ 31 weeks, Group B) were recruited for flicker ERG recording through closed eyelids using the RETeval® device and skin electrodes. Group A was tested within the first week of life and Group B between 34th and 37th week postmenstrual age. Flicker stimuli were presented at 28.3 Hz with stimulus levels of 3, 6, 12, 30 and 50 cd•s/m2. Primary endpoints were peak time (ms) and amplitude (µV). RESULTS: Flicker ERGs were recordable in most infants with the highest proportion of reproducible ERGs at 30 cd•s/m2. Amplitudes increased with stronger flicker stimulation, while peak times did not differ significantly between stimulus levels nor groups. Amplitudes were significantly greater in Group B at the strongest stimulus level (Mann-Whitney-U-Test=198.00, Z = 4.097, p = <0.001). CONCLUSIONS: Feasibility of collecting flicker ERG data in most preterm infants was confirmed. We found no evidence of reduced retinal responses to flicker stimuli associated with extreme prematurity. Higher amplitudes in very and extremely preterm infants could indicate acceleration of retinal development following birth, triggered by visual stimulation.