Developing a predictive model for metastatic potential in pancreatic neuroendocrine tumor.

CONTEXT: Pancreatic neuroendocrine tumors (PNETs) exhibit a wide range of behavior from localized disease to aggressive metastasis. A comprehensive transcriptomic profile capable of differentiating between these phenotypes remains elusive. OBJECTIVE: Use machine learning to develop predictive models of PNET metastatic potential dependent upon transcriptomic signature. METHODS: RNA-sequencing data were analyzed from 95 surgically-resected primary PNETs in an international cohort. Two cohorts were generated with equally balanced metastatic PNET composition. Machine learning was used to create predictive models distinguishing between localized and metastatic tumors. Models were validated on an independent cohort of 29 formalin-fixed, paraffin-embedded samples using NanoString nCounter®, a clinically-available mRNA quantification platform. RESULTS: Gene expression analysis identified concordant differentially expressed genes between the two cohorts. Gene set enrichment analysis identified additional genes that contributed to enriched biologic pathways in metastatic PNETs. Expression values for these genes were combined with an additional 7 genes known to contribute to PNET oncogenesis and prognosis, including ARX and PDX1. Eight specific genes (AURKA, CDCA8, CPB2, MYT1L, NDC80, PAPPA2, SFMBT1, ZPLD1) were identified as sufficient to classify the metastatic status with high sensitivity (87.5% - 93.8%) and specificity (78.1% - 96.9%). These models remained predictive of the metastatic phenotype using NanoString nCounter® on the independent validation cohort, achieving a median AUROC of 0.886. CONCLUSIONS: We identified and validated an eight-gene panel predictive of the metastatic phenotype in PNETs, which can be detected using the clinically-available NanoString nCounter® system. This panel should be studied prospectively to determine its utility in guiding operative versus non-operative management.

Patterns in the Reporting of Aggressive Histologic Subtypes in Papillary Thyroid Cancer.

INTRODUCTION: The tall cell, columnar, and diffuse sclerosing subtypes are aggressive histologic subtypes of papillary thyroid cancer (PTC) with increasing incidence, yet there is a wide variation in reporting. We aimed to identify and compare factors associated with the reporting of these aggressive subtypes (aPTC) to classic PTC (cPTC) and secondarily identify differences in outcomes. METHODS: The National Cancer Database was utilized to identify cPTC and aPTC from 2004 to 2017. Patient and facility demographics and clinicopathologic variables were analyzed. Independent predictors of aPTC reporting were identified and a survival analysis was performed. RESULTS: The majority of aPTC (67%) were reported by academic facilities. Compared to academic facilities, all other facility types were 1.4-2.0 times less likely to report aPTC (P < 0.05). Regional variation in reporting was noted, with more cases reported in the Middle Atlantic, despite there being more total facilities in the South Atlantic and East North Central regions. Compared to the Middle Atlantic, all other regions were 1.4-5 times less likely to report aPTC (P < 0.001). Patient characteristics including race and income were not associated with aPTC reporting. Compared to cPTC, aPTC had higher rates of aggressive features and worse 5-y overall survival (90.5% versus 94.5%, log rank P < 0.001). CONCLUSIONS: Aggressive subtypes of PTC are associated with worse outcomes. Academic and other facilities in the Middle Atlantic were more likely to report aPTC. This suggests the need for further evaluation of environmental or geographic factors versus a need for increased awareness and more accurate diagnosis of these subtypes.

Radioactive iodine administration is not associated with improved disease-specific survival in classic papillary thyroid carcinoma greater than 4 cm confined to the thyroid.

BACKGROUND: We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management. METHODS: The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival. RESULTS: There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39-1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69-7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02-1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm. CONCLUSION: Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.

COVID-19 outcomes in haemopoietic stem cell transplant recipients in Western Australia: the value of vaccination and antiviral therapy.

Coronavirus-19 (COVID-19) mortality rates among haemopoietic stem cell transplant (HSCT) patients are high, ranging between 20% and 40%. We prospectively evaluated the mortality outcomes of COVID-19 in Western Australian HSCT patients. A total of 32/492 (6.5%) HSCT recipients contracted COVID-19 during the study, of whom 30/32 (94%) developed mild or asymptomatic disease. Two allogeneic HSCT patients were hospitalised for severe COVID-19; one patient died. Stringent healthcare, social isolation practices, aggressive vaccination programmes and rapid access to COVID-19 antivirals may have promoted mild COVID-19 illness in Western Australian HSCT patients, resulting in one of the lowest COVID-19 mortality rates in HSCT recipients worldwide.

Discriminative potential of exhaled breath condensate biomarkers with respect to chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affecting 334 million people in the world remains a major cause of morbidity and mortality. Proper diagnosis of COPD is still a challenge and largely solely based on spirometric criteria. We aimed to investigate the potential of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) to discriminate COPD patients. METHODS: Three hundred three participants were randomly selected from a 15,000-transit worker cohort within the Respiratory disease Occupational Biomonitoring Collaborative Project (ROBoCoP). COPD was defined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second to Forced Vital Capacity < 0.7 in spirometry validated by an experienced pulmonologist. Discriminative power of biomarker profiles in EBC was analyzed using linear discriminant analyses. RESULTS: Amongst 300 participants with validated spirometry, 50.3% were female, 52.3 years old in average, 36.0% were current smokers, 12.7% ex-smokers with mean tobacco exposure of 15.4 pack-years. Twenty-one participants (7.0%) were diagnosed as COPD, including 19 new diagnoses, 12 of which with a mild COPD stage (GOLD 1). Amongst 8 biomarkers measured in EBC, combination of 2 biomarkers, Lactate and Malondialdehyde (MDA) significantly discriminated COPD subjects from non-COPD, with a 71%-accuracy, area under the receiver curve of 0.78 (p-value < 0.001), and a negative predictive value of 96%. CONCLUSIONS: These findings support the potential of biomarkers in EBC, in particular lactate and MDA, to discriminate COPD patients even at a mild or moderate stage. These EBC biomarkers present a non-invasive and drugless technique, which can improve COPD diagnosis in the future.

Partial Splenic Embolization in Paediatric Sickle Cell Disease Patients with Hypersplenism.

PURPOSE: To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD). MATERIAL AND METHODS: This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6 months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma. RESULTS: The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05 g/dL vs. 6.31 g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline. CONCLUSION: PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions.

Individual Patient Comorbidities and Effect on Cochlear Implant Performance.

OBJECTIVE: To examine the association between preoperative comorbidities and cochlear implant speech outcomes. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: A total of 976 patients who underwent cochlear implantation (CI) between January 2015 and May 2022. Adult patients with follow-up, preoperative audiologic data, and a standardized anesthesia preoperative note were included. EXPOSURE: Adult Comorbidity Evaluation 27 (ACE-27) based on standardized anesthesia preoperative notes. MAIN OUTCOME MEASURES: Postoperative change in consonant-nucleus-consonant (CNC) score, AzBio Sentence score in quiet, and AzBio + 10 dB signal-to-noise ratio (SNR). Sentence score of the implanted ear at 3, 6, and 12 months. RESULTS: A total of 560 patients met inclusion criteria; 112 patients (20%) had no comorbidity, 204 patients (36.4%) had mild comorbidities, 161 patients (28.8%) had moderate comorbidities, and 83 patients (14.8%) had severe comorbidities. Mixed model analysis revealed all comorbidity groups achieved a clinically meaningful improvement in all speech outcome measures over time. This improvement was significantly different between comorbidity groups over time for AzBio Quiet ( p = 0.045) and AzBio + 10 dB SNR ( p = 0.0096). Patients with severe comorbidities had worse outcomes. From preop to 12 months, the estimated marginal mean difference values (95% confidence interval) between the no comorbidity group and the severe comorbidity group were 52.3 (45.7-58.9) and 32.5 (24.6-40.5), respectively, for AzBio Quiet; 39.5 (33.8-45.2) and 21.2 (13.6-28.7), respectively, for AzBio + 10 dB SNR; and 43.9 (38.7-49.0) and 31.1 (24.8-37.4), respectively, for CNC. CONCLUSIONS: Comorbidities as assessed by ACE-27 are associated with CI performance. Patients with more severe comorbidities have clinically meaningful improvement but have worse outcome compared to patients with no comorbidities.

Low Mitotic Activity in Papillary Thyroid Cancer: A Marker for Aggressive Features and Recurrence.

CONTEXT: The significance of low mitotic activity in papillary thyroid cancer (PTC) is largely undefined. OBJECTIVE: We aimed to determine the behavioral landscape of PTC with low mitotic activity compared to that of no- and high-mitotic activity. METHODS: A single-institution consecutive series of PTC patients from 2018-2022 was reviewed. Mitotic activity was defined as no mitoses, low (1-2 mitoses/2 mm2) or high (≥3 mitoses/2 mm2) per the World Health Organization. The 2015 American Thyroid Association risk stratification was applied to the cohort, and clinicopathologic features were compared between groups. For patients with ≥6 months follow-up, Cox regression analyses for recurrence were performed. RESULTS: 640 PTCs were included - 515 (80.5%) no mitotic activity, 110 (17.2%) low mitotic activity, and 15 (2.3%) high mitotic activity. Overall, low mitotic activity exhibited rates of clinicopathologic features including vascular invasion, gross extrathyroidal extension, and lymph node metastases in between those of no- and high-mitotic activity. PTCs with low mitotic activity had higher rates of intermediate- and high-risk ATA risk stratification compared to those with no mitotic activity (p < 0.001). Low mitotic activity PTCs also had higher recurrence rates (15.5% vs. 4.5%, p < 0.001). Low mitotic activity was associated with recurrence, independent of the ATA risk stratification (HR 2.96; 95% CI 1.28-6.87, p = 0.01). CONCLUSIONS: Low mitotic activity is relatively common in PTC and its behavior lies within a spectrum between no- and high-mitotic activity. Given its association with aggressive clinicopathologic features and recurrence, low mitotic activity should be considered when risk stratifying PTC patients for recurrence.

Imaging flow cytometric detection of del(17p) in bone marrow and circulating plasma cells in multiple myeloma.

BACKGROUND: Detection of del(17p) in myeloma is generally performed by fluorescence in situ hybridization (FISH) on a slide with analysis of up to 200 nuclei. The small cell sample analyzed makes this a low precision test. We report the utility of an automated FISH method, called "immuno-flowFISH", to detect plasma cells with adverse prognostic risk del(17p) in bone marrow and blood samples of patients with myeloma. METHODS: Bone marrow (n = 31) and blood (n = 19) samples from 35 patients with myeloma were analyzed using immuno-flowFISH. Plasma cells were identified by CD38/CD138-immunophenotypic gating and assessed for the 17p locus and centromere of chromosome 17. Cells were acquired on an AMNIS ImageStreamX MkII imaging flow cytometer using INSPIRE software. RESULTS: Chromosome 17 abnormalities were identified in CD38/CD138-positive cells in bone marrow (6/31) and blood (4/19) samples when the percent plasma cell burden ranged from 0.03% to 100% of cells. Abnormalities could be identified in 14.5%-100% of plasma cells. CONCLUSIONS: The "immuno-flowFISH" imaging flow cytometric method could detect del(17p) in plasma cells in both bone marrow and blood samples of myeloma patients. This method was also able to detect gains and losses of chromosome 17, which are also of prognostic significance. The lowest levels of 0.009% (bone marrow) and 0.001% (blood) for chromosome 17 abnormalities was below the detection limit of current FISH method. This method offers potential as a new means of identifying these prognostically important chromosomal defects, even when only rare cells are present and for serial disease monitoring.

High-Performance Iridium-Molybdenum Oxide Electrocatalysts for Water Oxidation in Acid: Bayesian Optimization Discovery and Experimental Testing.

Ir oxides are costly and scarce catalysts for oxygen evolution reaction (OER) in acid. There has been extensive interest in developing alternatives that are either Ir-free or require smaller amounts of Ir to drive the reactions at acceptable rates. One design strategy is to identify Ir-based mixed oxides that achieve similar performance while requiring smaller amounts of Ir. The obstacle to this strategy has been a very large phase space of the Ir-based mixed metal oxides, in terms of the metals combined with Ir and the different crystallographic structures of the mixed oxides, which prevents a thorough exploration of possible materials. In this work, we developed a workflow that uses machine-learning-aided Bayesian optimization in combination with density functional theory to make the exploration of this phase space plausible. This screening identified Mo as a promising dopant for forming acid-tolerant Ir-based oxides for the OER. We synthesized and characterized the Ir-Mo mixed oxides in the form of thin-film electrocatalysts with a known surface area. We show that these mixed oxides exhibited overpotentials ∼30 mV lower than a pure Ir control while maintaining 24% lower Ir dissolution rates than the Ir control. These findings suggest that Mo is a promising dopant and highlight the promise of machine learning to guide the experimental exploration and optimization of catalytic materials.

Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis.

Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise de novo or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical "MF-like" morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of TCF3 in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.

What is the context? We investigated TCF3 (transcription factor 3), a gene that regulates megakaryocyte development, for genomic and proteomic changes in myelofibrosis.Myelofibrosis is the aggressive phase of a group of blood cancers called myeloproliferative neoplasms, and abnormalities in development and maturation of megakaryocytes is thought to drive the development of myelofibrosis.What is new? We report detection of three novel TCF3 mutations in megakaryocytes and decreases in TCF3 protein and gene expression in primary megakaryocytes and platelets from patients with myelofibrosis.This is the first association between loss of TCF3 in megakaryocytes from patients and myelofibrosis.What is the impact? TCF3 dysregulation may be a novel mechanism that is responsible for the development of myelofibrosis and better understanding of this pathway could identify new drug targets.

Accelerated Brain Atrophy, Microstructural Decline and Connectopathy in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) has recently been linked to cognitive impairment. We hypothesized that AMD modifies the brain aging trajectory, and we conducted a longitudinal diffusion MRI study on 40 participants (20 with AMD and 20 controls) to reveal the location, extent, and dynamics of AMD-related brain changes. Voxel-based analyses at the first visit identified reduced volume in AMD participants in the cuneate gyrus, associated with vision, and the temporal and bilateral cingulate gyrus, linked to higher cognition and memory. The second visit occurred 2 years after the first and revealed that AMD participants had reduced cingulate and superior frontal gyrus volumes, as well as lower fractional anisotropy (FA) for the bilateral occipital lobe, including the visual and the superior frontal cortex. We detected faster rates of volume and FA reduction in AMD participants in the left temporal cortex. We identified inter-lingual and lingual-cerebellar connections as important differentiators in AMD participants. Bundle analyses revealed that the lingual gyrus had a lower streamline length in the AMD participants at the first visit, indicating a connection between retinal and brain health. FA differences in select inter-lingual and lingual cerebellar bundles at the second visit showed downstream effects of vision loss. Our analyses revealed widespread changes in AMD participants, beyond brain networks directly involved in vision processing.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Timing to Surgery and Lymph Node Upstaging in Gastric Cancer: An NCDB Analysis.

BACKGROUND: Prior studies have shown tumor specificity on the impact of longer time interval from diagnosis to surgery, however in gastric cancer (GC) this remains unclear. We aimed to determine if a longer time interval from diagnosis to surgery had an impact on lymph node (LN) upstaging and overall survival (OS) outcomes among patients with clinically node negative (cN0) GC. PATIENTS AND METHODS: Patients diagnosed with cN0 GC undergoing surgery between 2004-2018 were identified in the National Cancer Database (NCDB) and divided into intervals between time of diagnosis and surgery [short interval (SI): ≥ 4 days to < 8 weeks and long interval (LI): ≥ 8 weeks]. Multivariable regression analysis evaluated the independent impact of surgical timing on LN upstaging and a Cox proportional hazards analysis and Kaplan-Meier curves evaluated survival outcomes. RESULTS: Of 1824 patients with cN0 GC, 71.8% had a SI to surgery and 28.1% had a LI to surgery. LN upstaging was seen more often in the SI group when compared to LI group (82% versus 76%, p = 0.004). LI to surgery showed to be an independent factor protective against LN upstaging [adjusted odds ratio = 0.62, 95% CI: (0.39-0.99)]. Multivariate Cox regression analysis indicated that time to surgery was not associated with a difference in overall survival [hazard ratio (HR) = 0.91, 95% CI: (0.71-1.17)], however uncontrolled Kaplan-Meier curves showed OS difference between the SI and LI to surgery groups (p = 0.037). CONCLUSION: Timing to surgery was not a predictor of LN upstaging or overall survival, suggesting that additional medical optimization in preparation for surgery and careful preoperative staging may be appropriate in patients with node negative early stage GC without affecting outcomes.

Identifying Slim Modiolar Electrode Tip Fold-Over With Intracochlear Electrocochleography.

OBJECTIVE: To evaluate the predictive value of intracochlear electrocochleography (ECochG) for identifying tip fold-over during cochlear implantation (CI) using the slim modiolar electrode (SME) array. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary referral center. METHODS: From July 2022 to June 2023, 142 patients, including adults and children, underwent intracochlear ECochG monitoring during and after SME placement. Tone-bursts were presented from 250 Hz to 2 kHz at 108 to 114 dB HL. A fast Fourier transform (FFT) allowed for frequency-specific evaluation of ECochG response. ECochG patterns during insertion and postinsertion were evaluated using sensitivity and specificity analysis to predict tip fold-over. Intraoperative plain radiographs served as a reference standard. RESULTS: Fifteen tip fold-over cases occurred (10.6%) with significant ECochG response (>2 µV). Sixty-one cases without tip fold-over occurred (43.0%) with significant ECochG response. All tip fold-overs had both a nontonotopic postinsertion sweep and nonrobust active insertion pattern. No patients with robust insertion or tonotopic sweep patterns had tip fold-over. Sensitivity of detecting tip fold-over when having both nonrobust insertion and nontonotopic sweep patterns was 100% (95% confidence inteval [CI] 78.2%-100%), specificity was 68.9% (95% CI 55.7%-80.1%), and the overall accuracy was 72.0% (95% CI 60.5%-81.7%). CONCLUSION: Intracochlear ECochG monitoring during cochlear implantation with the SME can be a valuable tool for identifying properly positioned electrode arrays. In cases where ECochG patterns are nonrobust on insertion and nontonotopic for electrode sweeps, there may be a concern for tip fold-over, and intraoperative imaging is necessary to confirm proper insertion.

Impedance planimetry (EndoFLIPTM) and surgical outcomes after Hill compared to Toupet fundoplication.

INTRODUCTION: Endoluminal functional lumen imaging probe (EndoFLIP) provides a real-time assessment of gastroesophageal junction (GEJ) compliance during fundoplication. Given the limited data on EndoFLIP measurements during the Hill procedure, we investigated the impact of the Hill procedure on GEJ compliance compared to Toupet fundoplication. METHODS: Patients who underwent robotic Hill or Toupet fundoplication with intraoperative EndoFLIP between 2017 and 2022 were included. EndoFLIP measurements of the GEJ included cross sectional surface area (CSA), intra-balloon pressure, high pressure zone length (HPZ), distensibility index (DI), and compliance. Subjective reflux symptoms, gastroesophageal reflux disease-health related quality of life (GERD-HRQL) score, and dysphagia score were assessed pre-operatively as well as at short- and longer-term follow-up. RESULTS: One-hundred and fifty-four patients (71.9%) had a Toupet fundoplication while sixty (28%) patients underwent the Hill procedure. The CSA [27.7 ± 10.9 mm2 vs 42.2 ± 17.8 mm2, p < 0.0001], pressure [29.5 ± 6.2 mmHg vs 33.9 ± 8.5 mmHg, p = 0.0009], DI [0.9 ± 0.4 mm2/mmHg vs 1.3 ± 0.6 mm2/mmHg, p = 0.001], and compliance [25.9 ± 12.8 mm3/mmHg vs 35.4 ± 13.4 mm3/mmHg, p = 0.01] were lower after the Hill procedure compared to Toupet. However, there was no difference in post-fundoplication HPZ between procedures [Hill: 2.9 ± 0.4 cm, Toupet: 3.1 ± 0.6 cm, p = 0.15]. Follow-up showed no significant differences in GERD-HRQL scores, overall dysphagia scores or atypical symptoms between groups (p > 0.05). CONCLUSION: The Hill procedure is as effective to the Toupet fundoplication in surgically treating gastroesophageal reflux disease (GERD) despite the lower CSA, DI, and compliance after the Hill procedure. Both procedures led to DI < 2 mm2/mmHg with no significant differences in dysphagia reporting (12-24) months after the procedure. Further studies to elucidate a cutoff value for DI for postoperative dysphagia development are still warranted.

A Morrison stem gekkotan reveals gecko evolution and Jurassic biogeography.

Geckos are a speciose and globally distributed clade of Squamata (lizards, including snakes and amphisbaenians) that are characterized by a host of modifications for nocturnal, scansorial and insectivorous ecologies. They are among the oldest divergences in the lizard crown, so understanding the origin of geckoes (Gekkota) is essential to understanding the origin of Squamata, the most species-rich extant tetrapod clade. However, the poor fossil record of gekkotans has obscured the sequence and timing of the assembly of their distinctive morphology. Here, we describe the first North American stem gekkotan based on a three-dimensionally preserved skull from the Morrison Formation of western North America. Despite its Late Jurassic age, the new species already possesses several key characteristics of the gekkotan skull along with retained ancestral features. We show that this new stem gekkotan, and several previously named species of uncertain phylogenetic relationships, comprise a widespread clade of early crown lizards, substantiating faunal homogeneity in Laurasia during the Late Jurassic that extended across disparate ecological, body-size and physiological classes.