Potential Microemboli Formation Risk and its Management during the Heated Saline Enhanced Radiofrequency (SERF) Needle-tip Catheter Ablation.

BACKGROUND: The potential risk of embolic events during ablation in the left ventricle (LV) with a heated saline-enhanced radiofrequency needle-tip ablation catheter (SERF) has not been characterized. OBJECTIVE: This study aims to investigate formation of microemboli or other untoward events during SERF ablation. METHODS: Ninety-three radiofrequency (RF) ablations were performed in the LV of 14 pigs using a SERF (35W, 70 sec and 60°C normal or degassed saline [NS or DS] irrigation with a flow rate of 10mL/min) versus a standard irrigated-tip RF catheter (S-RF) (30 or 50W, 30sec, and 17ml/min). Microbubble formation was graded based on intracardiac echography (ICE). Microbubbles, microembolic signals and microparticles were monitored using our established model. RESULTS: There was no significant difference in microbubble volume among SERF-NS, SERF-DS and S-RF 30W with "Grade 1" ICE microbubble grade (0.201µL [0.011-3.13], 0.455µL [0.06-2.66] and 0.004µL [0.00-0.16], median [quartiles], respectively). There was no significant difference in microembolic signals among SERF-NS, SERF-DS, and S-RF 30W with "Grade 1" bubbles (n=8.0±5.8, 7.6±4.2 and 6.1±6.1, respectively). Both SERF-NS and SERF-DS created larger lesions than both S-RF 30 and 50W deliveries (1241.5±658.6mm3, 1497.7±893.4mm3, 75.0±24.8mm3 and 184.0±93.8mm3, mean±standard deviation, p<0.001). There was no significant difference in the microparticle incidence among groups (p=0.675). No evidence of embolic events was found in the brain and other organs at the histology assessment. CONCLUSIONS: In the setting of SERF ablation, significantly large LV lesion can be created without any increment in embolic microbubble or particle events. Grade 1 microbubble is related to the efficacy and safety.

Heartburn Relief Is the Major Unmet Need for Drug Development in Gastroesophageal Reflux Disease: Threshold Value Analysis.

BACKGROUND AND AIMS: Heartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment. METHODS: A decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported. RESULTS: Without insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts. DISCUSSION: We demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.

Optimizing the Management Algorithm for Adults With Functional Constipation Failing a Fiber/Laxative Trial in General Gastroenterology: Cost-Effectiveness and Cost-Minimization Analysis.

INTRODUCTION: Anorectal function testing is traditionally relegated to subspecialty centers. Yet, it is an office-based procedure that appears capable of triaging care for the many patients with Rome IV functional constipation that fail empiric over-the-counter therapy in general gastroenterology, as an alternative to empirical prescription drugs. We aimed to evaluate cost-effectiveness of routine anorectal function testing in this specific population. METHODS: We performed a cost-effectiveness analysis from the patient perspective and a cost-minimization analysis from the insurer perspective to compare 3 strategies: (i) empiric prescription drugs followed by pelvic floor physical therapy (PFPT) for drug failure, (ii) empiric PFPT followed by prescription drugs for PFPT failure, or (iii) care directed by up-front anorectal function testing. Model inputs were derived from systematic reviews of prospective clinical trials, national cost data sets, and observational cohort studies of the impact of chronic constipation on health outcomes, healthcare costs, and work productivity. RESULTS: The most cost-effective strategy was upfront anorectal function testing to triage patients to appropriate therapy, in which the subset of patients without anal hypocontractility on anorectal manometry and with a balloon expulsion time of at least 6.5 seconds would be referred to PFPT. In sensitivity analysis, empiric PFPT was more cost effective than empiric prescription drugs except for situations in which the primary goal of treatment was to increase bowel movement frequency. If adopted, gastroenterologists would refer ∼17 patients per year to PFPT, supporting feasibility. DISCUSSION: Anorectal function testing seems to be an emergent technology to optimize cost-effective outcomes, overcoming testing costs by phenotyping care.

Sertoli cell-enriched proteins in mouse and human testicular interstitial fluid.

Sertoli cells support the development of sperm and the function of various somatic cells in the interstitium between the tubules. Sertoli cells regulate the function of the testicular vasculature and the development and function of the Leydig cells that produce testosterone for fertility and virility. However, the Sertoli cell-derived factors that regulate these cells are largely unknown. To define potential mechanisms by which Sertoli cells could support testicular somatic cell function, we aimed to identify Sertoli cell-enriched proteins in the testicular interstitial fluid (TIF) between the tubules. We previously resolved the proteome of TIF in mice and humans and have shown it to be a rich source of seminiferous tubule-derived proteins. In the current study, we designed bioinformatic strategies to interrogate relevant proteomic and genomic datasets to identify Sertoli cell-enriched proteins in mouse and human TIF. We analysed proteins in mouse TIF that were significantly reduced after one week of acute Sertoli cell ablation in vivo and validated which of these are likely to arise primarily from Sertoli cells based on relevant mouse testis RNASeq datasets. We used a different, but complementary, approach to identify Sertoli cell-enriched proteins in human TIF, taking advantage of high-quality human testis genomic, proteomic and immunohistochemical datasets. We identified a total of 47 and 40 Sertoli cell-enriched proteins in mouse and human TIF, respectively, including 15 proteins that are conserved in both species. Proteins with potential roles in angiogenesis, the regulation of Leydig cells or steroidogenesis, and immune cell regulation were identified. The data suggests that some of these proteins are secreted, but that Sertoli cells also deposit specific proteins into TIF via the release of extracellular vesicles. In conclusion, we have identified novel Sertoli cell-enriched proteins in TIF that are candidates for regulating somatic cell-cell communication and testis function.

Esophageal motility in systemic sclerosis before and after autologous hematopoietic cell transplantation.

INTRODUCTION: Systemic sclerosis (SSc) is associated with esophageal dysmotility. Autologous hematopoietic cell transplantation (HCT) results in improvement of skin tightness and lung function. Whether esophageal motility improves after HCT is unknown. METHODS: Esophageal motility was studied using high-resolution esophageal manometry in 21 SSc patients before and at multiple time points after autologous HCT. Median posttransplant follow-up was 2 years (range, 6 months to 5 years). RESULTS: Prior to HCT, all 21 patients had abnormal motility-10 (48%) had unmeasurable and 11 (52%) had measurable peristalsis. Manometric diagnosis in the former 10 patients was "absent contractility" and in the latter 11 patients "ineffective esophageal motility (IEM)." After HCT, among the 10 patients with absent contractility, 9 continued to have absent contractility and one demonstrated weak measurable peristalsis. Of the 11 patients with IEM, 5 experienced SSc relapse, and 2 out of these 5 patients developed absent contractility. Among the 6 non-relapsed patients, 4 continued to have IEM, and 2 developed normal motility. CONCLUSIONS: HCT appears to have no beneficial effect on motility in patients with unmeasurable peristalsis. In patients with measurable peristalsis, HCT appears to stabilize and in some normalize motility, unless relapse occurs. Key Points • In patients with systemic sclerosis, esophageal dysmotility is a significant contributor to morbidity and so far, there has been no data describing the effects of hematopoietic cell transplantation on esophageal motility. • Our work demonstrated that in patients with systemic sclerosis and unmeasurable esophageal peristalsis prehematopoietic cell transplantation, there was no measurable beneficial effect of transplantation on esophageal motility. • In patients with systemic sclerosis and measurable peristalsis prehematopoietic cell transplantation, esophageal motility stabilized, except in relapsed patients.

Chronic Pain and Mood Disorders Are Not Barriers to Symptom Improvement Under Collaborative Co-managed Care (C3).

OBJECTIVES: Patients with comorbid chronic pain and mood disorders have more severe gastrointestinal disease and higher healthcare expenses than their peers. We sought to determine whether management under our innovative Collaborative Co-Managed Care (C3) general gastroenterology care model improved outcomes. METHODS: Patient questionnaires completed by outpatients at our GI Motility Center were analyzed alongside demographic information to determine predictors of response to treatment based on adequate relief of gastrointestinal symptoms and improvement in quality of life. RESULTS: These comorbidities did not significantly impair response and may be associated with improved response under our model. CONCLUSIONS: The C3 general gastroenterology care model anchors on setting expectations and team-based communication and improves outcomes of, and access to, care.

Pseudocholinesterase deficiency in ophthalmology: a systematic review.

PURPOSE: Unexpected anesthesia-related complications are among the most feared outcomes of ambulatory surgery. One potential culprit is pseudocholinesterase deficiency, which most commonly presents with protracted apnea, necessitating prolonged mechanical ventilation. We report the first case of pseudocholinesterase deficiency in a Bengali person and the first systematic review of pseudocholinesterase deficiency in ophthalmology. This review analyzed the epidemiology, etiologies, presentation, evaluation, and treatment of pseudocholinesterase deficiency. METHODS: Searches were conducted in PubMed, Embase, and Medline through August of 2022 for publications related to pseudocholinesterase deficiency in ophthalmology. In total, 689 studies were screened by two independent reviewers with 26 full-text articles examined for inclusion eligibility. Nineteen studies were eligible and included in the final analysis. RESULTS: Of the 16 identified cases of pseudocholinesterase deficiency, nine (56%) were drug-induced, four (25%) were inherited deficiencies, and in one (6%) of the cases, the cause could not be determined. In two (13%) cases, pseudocholinesterase deficiency could not be confirmed or ruled out. The duration of post-operative apnea ranged from 10 minutes to 14 hours. Continued ventilatory support was the main treatment for all cases and all patients made a full recovery. CONCLUSIONS: Pseudocholinesterase deficiency is a rare, but potentially fatal, anesthetic complication that results in prolonged apnea, respiratory distress, and dependency on ventilators. Ophthalmologists should remain aware of this condition, especially when planning outpatient procedures, as ambulatory centers may have limited resources for managing prolonged post-operative complications.

An Office-Based, Point-of-Care Test Predicts Treatment Outcomes With Community-Based Pelvic Floor Physical Therapy in Patients With Chronic Constipation.

BACKGROUND & AIMS: Rectal evacuation disorders are common among constipated patients. We aimed to evaluate the accuracy of an investigational point-of-care test (rectal expulsion device [RED]) to predict outcomes with community-based pelvic floor physical therapy. METHODS: We enrolled patients meeting Rome IV criteria for functional constipation failing fiber/laxatives for more than 2 weeks. RED was inserted and self-inflated, and then time-to-expel was measured in a left lateral position. All patients underwent empiric community-based pelvic floor physical therapy in routine care with outcomes measured at 12 weeks. The primary end point was global clinical response (Patient Assessment of Constipation Symptoms score reduction, >0.75 vs baseline). Secondary end points included improvement in health-related quality-of-life (Patient Assessment of Constipation Quality of Life score reduction, >1.0) and complete spontaneous bowel movement frequency (Food and Drug Administration complete spontaneous bowel movement responder definition). RESULTS: Thirty-nine patients enrolled in a feasibility phase to develop the use-case protocol. Sixty patients enrolled in a blinded validation phase; 52 patients (mean, 46.9 y; 94.2% women) were included in the intention-to-treat analysis. In the left lateral position, RED predicted global clinical response (generalized area under the curve [gAUC], 0.67; 95% CI, 0.58-0.76]), health-related quality-of-life response (gAUC, 0.67; 95% CI, 0.58-0.77; P < .001), and complete spontaneous bowel movement response (gAUC, 0.63; 95% CI, 0.57-0.71; P < .001). As a screening test, a normal RED effectively rules out evacuation disorders (expected clinical response, 8.9%; P = .042). Abnormal RED in the left lateral position (defined as expulsion within 5 seconds or >120 seconds) predicted 48.9% clinical response to physical therapy. A seated maneuver enhanced the likelihood of clinical response (71.1% response with seated RED retained >13 seconds) but likely is unnecessary in most settings. CONCLUSIONS: RED offers an opportunity to disrupt the paradigm by offering a personalized approach to managing chronic constipation in the community (Clinicaltrials.gov: NCT04159350).

Utility of Anorectal Testing to Predict Outcomes With Pelvic Floor Physical Therapy in Chronic Constipation: Pragmatic Trial.

BACKGROUND & AIMS: We performed a clinical trial that aimed to inform the clinical utility of anorectal manometry (ARM) and balloon expulsion time (BET) as up-front tests to predict outcomes with community-based pelvic floor physical therapy as the next best step to address chronic constipation after failing an empiric trial of soluble fiber supplementation or osmotic laxatives. METHODS: We enrolled 60 treatment-naïve patients with Rome IV functional constipation failing 2 weeks of soluble fiber supplementation or osmotic laxatives. All patients underwent ARM/BET (London protocol) followed by community-based pelvic floor physical therapy. Outcomes were assessed at baseline and 12 weeks. The primary end point was clinical response (Patient Assessment of Constipation-Symptoms instrument). RESULTS: Fifty-three patients completed pelvic rehabilitation and the post-treatment questionnaire. Contemporary frameworks define dyssynergia on balloon expulsion time and dyssynergic patterns (ARM), but these parameters did not inform clinical outcomes (area under the curve [AUC], <0.6). Squeeze pressure (>192.5 mm Hg on at least 1 of 3 attempts; sensitivity, 47.6%; specificity, 83.9%) and limited squeeze duration (inability to sustain 50% of squeeze pressure for >20 seconds; sensitivity, 71.4%; specificity, 58.1%) were the strongest predictors of clinical outcomes. Combining BET with squeeze duration (BET greater than 6.5 seconds and limited squeeze duration) improved predictive accuracy (AUC, 0.75; 95% CI, 0.59-0.90). BET poorly predicted outcomes as a single test (AUC, 0.54; 95% CI, 0.38-0.69). CONCLUSIONS: Using ARM to evaluate squeeze profiles, rather than dyssynergia, appears useful to screen patients with chronic constipation for up-front pelvic floor physical therapy based on likelihood of response. BET appears noninformative as a single screening test (ClinicalTrials.gov: NCT04159350).

Video-Based Deep Learning to Detect Dyssynergic Defecation with 3D High-Definition Anorectal Manometry.

BACKGROUND: We developed a deep learning algorithm to evaluate defecatory patterns to identify dyssynergic defecation using 3-dimensional high definition anal manometry (3D-HDAM). AIMS: We developed a 3D-HDAM deep learning algorithm to evaluate for dyssynergia. METHODS: Spatial-temporal data were extracted from consecutive 3D-HDAM studies performed between 2018 and 2020 at Dartmouth-Hitchcock Health. The technical procedure and gold standard definition of dyssynergia were based on the London consensus, adapted to the needs of 3D-HDAM technology. Three machine learning models were generated: (1) traditional machine learning informed by conventional anorectal function metrics, (2) deep learning, and (3) a hybrid approach. Diagnostic accuracy was evaluated using bootstrap sampling to calculate area-under-the-curve (AUC). To evaluate overfitting, models were validated by adding 502 simulated defecation maneuvers with diagnostic ambiguity. RESULTS: 302 3D-HDAM studies representing 1208 simulated defecation maneuvers were included (average age 55.2 years; 80.5% women). The deep learning model had comparable diagnostic accuracy [AUC 0.91 (95% confidence interval 0.89-0.93)] to traditional [AUC 0.93(0.92-0.95)] and hybrid [AUC 0.96(0.94-0.97)] predictive models in training cohorts. However, the deep learning model handled ambiguous tests more cautiously than other models; the deep learning model was more likely to designate an ambiguous test as inconclusive [odds ratio 4.21(2.78-6.38)] versus traditional/hybrid approaches. CONCLUSIONS: Deep learning is capable of considering complex spatial-temporal information on 3D-HDAM technology. Future studies are needed to evaluate the clinical context of these preliminary findings.

Clinical History Does Not Reliably Predict Clinical Outcomes With Pelvic Floor Physical Therapy to Treat Chronic Constipation.

Chronic constipation affects 10%-20% of the population and impacts quality-of-life similarly to rheumatoid arthritis or congestive heart failure.1 We recently showed in a prospective clinical trial that up-front, community-based pelvic floor physical therapy is effective to treat chronic constipation for patients seeking general gastroenterology care after failing a brief trial of osmotic laxative or soluble fiber supplementation2 and can be guided by anorectal function testing.3,4 In this post hoc analysis, we aimed to evaluate whether factors on clinical history including specific symptoms, work-productivity impairment, health-related quality-of-life impairment, and psychological factors are useful to inform patient selection on the expected likelihood of clinical response without using anorectal function tests.

Skin Color Representation in Ophthalmology Textbooks.

Objective: Inadequate diversity in dermatologic images has been associated with diagnostic delays and poorer health outcomes. This underrepresentation of darker skin tones has also been demonstrated across various fields of medicine, including rheumatology, urology, and in the COVID-19 pandemic. The distribution of skin tones has not been examined in educational ophthalmology texts. The authors aimed to quantify the representation of skin tones across three leading ophthalmology textbooks. Methods: Two independent investigators utilized the Fitzpatrick's skin phototype scale to code images containing skin as either "light" (Fitz. I-IV) or "dark" (Fitz. V-VI) in three fundamental ophthalmology textbooks: Clinical Ophthalmology (Salmon and Kanski), Ophthalmology (Yanoff and Duker), and the 13 Basic and Clinical Science Course texts by the American Academy of Ophthalmology. Images without discernible skin color were excluded. Results: Of the 9766 images reviewed, 2305 images met inclusion criteria. The three textbooks combined were found to have 2123 (92.1%) images of light skin tones and 182 images (7.9%) of dark skin tones. When compared to national data that found 12.6% of individuals to have dark skin tones, the proportion of images with darker skin tones in ophthalmology textbooks was statistically significantly lower (χ 2 corr(1, N = 4996) = 211.7, p < 0.001). Conclusions: Darker skin tones are statistically significantly underrepresented in textbooks that are central to education of trainees in ophthalmology. Acknowledgement and inclusion of skin tone diversity in ophthalmology educational materials are necessary to ensure that physicians in the field are equipped with the knowledge and training to provide the highest level of care to all patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01636-4.

Ablation of Refractory Ventricular Tachycardia Using Intramyocardial Needle Delivered Heated Saline-Enhanced Radiofrequency Energy: A First-in-Man Feasibility Trial.

BACKGROUND: Ablation of ventricular tachycardia (VT) is limited by the inability to create penetrating lesions to reach intramyocardial origins. Intramural needle ablation using in-catheter, heated saline-enhanced radio frequency (SERF) energy uses convective heating to increase heat transfer and produce deeper, controllable lesions at intramural targets. This first-in-human trial was designed to evaluate the safety and efficacy of SERF needle ablation in patients with refractory VT. METHODS: Thirty-two subjects from 6 centers underwent needle electrode ablation. Each had recurrent drug-refractory monomorphic VT after implantable cardioverter defibrillator implantation and prior standard ablation. During the SERF study procedure, one or more VTs were induced and mapped. The SERF needle catheter was used to create intramural lesions at targeted VT site(s). Acute procedural success was defined as noninducibility of the clinical VT after the procedure. Patients underwent follow-up at 30 days, and 3 and 6 months, with implantable cardioverter defibrillator interrogation at follow-up to determine VT recurrence. RESULTS: These refractory VT patients (91% male, 66±10 years, ejection fraction 35±11%; 56% ischemic, and 44% nonischemic) had a median of 45 device therapies (shock/antitachycardia pacing) for VT in the 3 to 6 months pre-SERF ablation. The study catheter was used to deliver an average of 10±5 lesions per case, with an average of 430±295 seconds of radiofrequency time, 122±65 minute of catheter use time, and a procedural duration of 4.3±1.3 hours. Acute procedural success was 97% for eliminating the clinical VT. At average follow-up of 5 months (n=32), device therapies were reduced by 89%. Complications included 2 periprocedural deaths: an embolic mesenteric infarct and cardiogenic shock, 2 mild strokes, and a pericardial effusion treated with pericardiocentesis (n=1). CONCLUSIONS: Intramural heated saline needle ablation showed complete acute and satisfactory mid-term control of difficult VTs failing 1 to 5 prior ablations and drug therapy. Further study is warranted to define safety and longer-term efficacy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT03628534 and NCT02994446.

A Parent Survey Assessing Association of Exposure to Gun Violence, Beliefs, and Physician Counseling.

OBJECTIVES: The study objectives are to assess associations between hospitalized children's parental exposure to gun violence (GV) and parental beliefs about guns and gun safety; secondarily, the authors aim to describe parental views on the pediatrician's role in firearm injury prevention (FIP) counseling. METHODS: Parents residing with children <20 years old hospitalized at a quaternary care hospital in a large city were eligible. Researchers administered verbal surveys between March 2017 and July 2019. We analyzed data (Wilcoxon rank-sum, χ2, or Fisher's exact tests, as appropriate) to compare the characteristics of those with exposure to GV and those without, and to assess associations of those with and without GV exposure with various beliefs. RESULTS: Enrollment included 225 parents or guardians. Although 75.5% agreed pediatricians should talk to parents about safe gun storage, 8.9% reported FIP counseling by their child's doctor. There were no substantial differences in characteristics between those with GV exposure versus those without. The study revealed that 60.0% of participants reported hearing gunshots, and 41.8% had a friend/relative who had been shot; only 29.8% reported neither. There were no differences between groups in gun-related beliefs regardless of exposure. CONCLUSIONS: In this population, there was no association between exposure to GV and gun-related beliefs. Most parents are receptive to FIP counseling, yet few have discussed FIP with their pediatrician despite high exposure to GV in this community. Nearly all parents agreed with the use of gunlocks and stricter laws for background checks. Regardless of exposure to GV, parents agreed with safe gun storage and support strengthening gun safety laws.

Leukemia inhibitory factor-receptor signalling negatively regulates gonadotrophin-stimulated testosterone production in mouse Leydig Cells.

Testicular Leydig cells (LCs) are the principal source of circulating testosterone in males. LC steroidogenesis maintains sexual function, fertility and general health, and is influenced by various paracrine factors. The leukemia inhibitory factor receptor (LIFR) is expressed in the testis and activated by different ligands, including leukemia inhibitory factor (LIF), produced by peritubular myoid cells. LIF can modulate LC testosterone production in vitro under certain circumstances, but the role of consolidated signalling through LIFR in adult LC function in vivo has not been established. We used a conditional Lifr allele in combination with adenoviral vectors expressing Cre-recombinase to generate an acute model of LC Lifr-KO in the adult mouse testis, and showed that LC Lifr is not required for short term LC survival or basal steroidogenesis. However, LIFR-signalling negatively regulates steroidogenic enzyme expression and maximal gonadotrophin-stimulated testosterone biosynthesis, expanding our understanding of the intricate regulation of LC steroidogenic function.

Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells.

Leydig cells (LC) are the main testicular androgen-producing cells. In eutherian mammals, two types of LCs emerge successively during testicular development, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). Both display significant differences in androgen production and regulation. Using bulk RNA sequencing, we compared the transcriptomes of both LC populations to characterize their specific transcriptional and functional features. Despite similar transcriptomic profiles, a quarter of the genes show significant variations in expression between FLCs and ALCs. Non-transcriptional events, such as alternative splicing was also observed, including a high rate of intron retention in FLCs compared to ALCs. The use of single-cell RNA sequencing data also allowed the identification of nine FLC-specific genes and 50 ALC-specific genes. Expression of the corticotropin-releasing hormone 1 (Crhr1) receptor and the ACTH receptor melanocortin type 2 receptor (Mc2r) specifically in FLCs suggests a dual regulation of steroidogenesis. The androstenedione synthesis by FLCs is stimulated by luteinizing hormone (LH), corticotrophin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) whereas the testosterone synthesis by ALCs is dependent exclusively on LH. Overall, our study provides a useful database to explore LC development and functions.

A Randomized Controlled Trial for Parents of Hospitalized Children: Keeping Kids Safe From Guns.

OBJECTIVES: To assess an educational intervention (BeSMART) for parents of hospitalized children on behaviors, beliefs, and knowledge about firearm safety. METHODS: A randomized controlled, 3-arm preintervention and postintervention study compared BeSMART video and handout interventions (with and without physician review) to tobacco smoke videos and handouts (control) on parental behaviors, beliefs, and knowledge. Eligibility criteria included parents and/or guardians residing with hospitalized children aged <20 years. The primary outcome was a change in parent-reported frequency of asking about guns in homes visited by their children preintervention to 1 month after intervention. Secondary outcomes were parent-reported likelihood of asking about guns in others' homes immediately postintervention and change in firearm safety beliefs and/or knowledge in the intervention versus control group, analyzed with analysis of variance. McNemar's and paired t tests compared changes within groups, and generalized estimating equations compared change between groups for the primary outcome. RESULTS: A total of 225 participants enrolled. Both intervention and control groups revealed significant increase mean in parent-reported Likert score of frequency of asking about guns within groups preintervention to 1 month after intervention (BeSMART: 1.5 to 2.3, P = .04; BeSMART + physician review: 1.4 to 1.9, P = .03; control: 1.4 to 2.3, P = .01). Change between groups was not significant (P = .81). Immediately postintervention, intervention groups reported higher likelihood of asking about guns (P < .001). Study groups revealed no significant differences in beliefs. Firearm safety knowledge increased significantly in the intervention groups. CONCLUSIONS: BeSMART firearm injury prevention intervention in a hospital setting increased parental knowledge regarding firearm safety. Immediately postintervention, BeSMART groups reported higher likelihood of asking about guns in others' homes compared with controls. At 1 month after intervention, all groups reported increased frequency asking about guns. Future investigations are needed to understand the duration of intervention impact.

Real-time intracardiac echocardiography validation of saline-enhanced radiofrequency needle-tip ablation: lesion characteristics and gross pathology correlation.

AIMS: With the implementation of saline-enhanced radiofrequency (SERF) needle-tip ablation, real-time validation of lesion formation is needed for the controllable creation of transmural lesions. The aim of the study was to analyse the ability of two-dimensional intracardiac echocardiography (2D-ICE) to guide and validate SERF ablation in real-time. METHODS AND RESULTS: Fifty-six SERF energy deliveries at left ventricular sites of 11 dogs guided by 2D-ICE were analysed (power: 15-50 W; time: 25-120 s; irrigation saline: 60°C with 10 mL/min flow rate). Catheter tip/tissue orientation and lesion formation could be well detected by 2D-ICE in 49 (87.5%) energy deliveries. Gross pathology analysis confirmed excellent 2D-ICE lesion localization, the ability to detect transmural lesions (70% sensitivity, 47% specificity) and positive correlation between 2D-ICE and the corresponding gross pathology measurements of 'maximal lesion depth'; (repeated measures correlation: rrm = 0.43, P = 0.012) and 'depth at maximal lesion width' (D@MW; rrm = 0.51, P = 0.003). The median angle between SERF catheter tip and endocardium was 76° [interquartile range (IQR) 58-83°]. The more perpendicular the catheter tip/tissue orientation was the deeper D@MW (rrm = 0.32, P = 0.045). Grade 3 microbubbles on 2D-ICE during ablation, indicating inadequate catheter tip/tissue contact, was associated with smaller lesion volumes than with Grade 1 microbubbles (284.8 mm3 [IQR 151.3-343.1] vs. 2114.1 mm3 [IQR 1437.0-3026.3], P < 0.001). CONCLUSION: With excellent lesion localization and a 70% detection rate of transmural lesions, 2D-ICE is well suited to validate SERF ablation lesion formation in real-time. The catheter tip/tissue angle impacts the lesion formation and through perpendicular catheter positioning, deeper intramural areas of the myocardium can be reached.