TFCP2 is a transcriptional regulator of heparan sulfate assembly and melanoma cell growth.

Heparan sulfate (HS) is a long, linear polysaccharide that is ubiquitously expressed in all animal cells and plays a key role in many cellular processes, including cell signaling and development. Dysregulation of HS assembly has been implicated in pathophysiological conditions, such as tumorigenesis and rare genetic disorders. HS biosynthesis occurs in a non-template-driven manner in the endoplasmic reticulum and Golgi through the activity of a large group of biosynthetic enzymes. While much is known about its biosynthesis, little is understood about the regulation of HS assembly across diverse tissue types and disease states. To address this gap in knowledge, we recently performed genome-wide CRISPR/Cas9 screens to identify novel regulatory factors of HS biosynthesis. From these screens, we identified the alpha globin transcription factor, TFCP2, as a top hit. To investigate the role of TFCP2 in HS assembly, we targeted TFCP2 expression in human melanoma cells using the CRISPR/Cas9 system. TFCP2 knockout cells exhibited decreased fibroblast growth factor binding to cell surface HS, alterations in HS composition, and slowed cell growth compared to wild-type cells. Additionally, RNA sequencing revealed that TFCP2 regulates the expression of multiple enzymes involved in HS assembly, including the secreted endosulfatase, SULF1. Pharmacological targeting of TFCP2 activity similarly reduced growth factor binding and increased SULF1 expression, and the knockdown of SULF1 expression in TFCP2 mutant cells restored melanoma cell growth. Overall, these studies identify TFCP2 as a novel transcriptional regulator of HS and highlight HS-protein interactions as a possible target to slow melanoma growth.

Impact of adrenal surgeon volume on outcome: analysis of 4464 operations from the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS).

BACKGROUND: There is a surgeon volume-outcome effect in adrenal surgery but the threshold for high-volume surgeon remains controversial. This study aimed to determine predictors of high-risk adrenal operations and to explore whether these should be restricted to high-volume surgeons. METHODS: Patients undergoing adrenal surgery and registered in the United Kingdom Registry of Endocrine and Thyroid Surgery between 2004 and 2021 were analysed. Outcomes included postoperative complications, duration of hospital stay, and mortality. Factors included in multivariable analysis were age, sex, diagnosis, surgical approach, laterality, and surgeon volume. Patients with missing data were excluded. RESULTS: A total of 4464 of 6174 patients (72.3%) were analysed. Postoperative complications occurred in 418 patients (9.4%) and 14 (0.3%) died. Median duration of hospital stay was 3 (i.q.r. 2-5) days. Co-variables significantly associated with an increase or decrease in postoperative complications (P < 0.050) were age (OR 1.02, 95% c.i. 1.01 to 1.03), adrenal cancer (OR 1.64, 1.14 to 2.36), minimally invasive approach (OR 0.317, 0.248 to 0.405), bilateral surgery (OR 1.66, 1.03 to 2.69), and surgeon volume (OR 0.98, 0.96 to 0.99). An increase or decrease in mortality was associated with patient age (OR 1.08, 1.03 to 1.13), minimally invasive approach (OR 0.08, 0.02 to 0.27), and bilateral surgery (OR 6.93, 1.40 to 34.34). The incidence of postoperative complications was significantly lower above a threshold of 12 operations per year (P = 0.034) and 20 per year (P < 0.001), but not six per year (P = 0.540). Median duration of hospital stay was 2 days for surgeons doing over 20 operations per year, compared with 3 days for those undertaking fewer than 20, fewer than 12 or fewer than 6 operations per year. CONCLUSION: Increasing surgical volume is associated with shorter hospital stay and fewer complications. This analysis supports the case for centralization of surgery for adrenal cancer and bilateral tumours to higher-volume surgeons performing a minimum of 12 operations per year.

The adrenal glands are found in the fatty tissue at the back of the abdomen above each kidney, and produce steroid and adrenaline hormones. Surgery on tumours of the adrenal gland is uncommon compared with surgery for other tumours such as those of the breast, bowel, kidney, and lung. Research has shown that the more adrenal operations a surgeon undertakes per year, the better the overall outcomes for patients undergoing that type of surgery. In this study, the outcomes from adrenal operations recorded over 18 years in the national adrenal surgical registry by members of the British Association of Endocrine and Thyroid Surgeons were analysed. The results confirmed previous findings showing that postoperative complications and length of hospital stay were reduced for patients operated by surgeons who did more adrenal operations per year. Operations done by keyhole surgery had better outcomes. Operations done either in older patients, or for the rare adrenal cancer tumours had worse outcomes, as did operations in which both adrenal glands were removed. The authors recommended that all surgeons performing adrenal surgery should monitor the outcomes of their operations, ideally in a national registry, and discuss these with patients before surgery; and undertake a minimum of 6 adrenal operations per year, but a minimum of 12 per year if doing surgery for adrenal cancer or surgery to remove both adrenal glands.

Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review.

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle-Ottawa Scale, with results analyzed descriptively. RESULTS: From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs. DISCUSSION: The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies. CONCLUSION: Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population. IMPACT: 1. Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates. 2. Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates. 3. The impact of the study lies in its potential to increase researchers' awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

Decreased erythrocyte aggregation in Glenn and Fontan: univentricular circulation as a rheologic disease model.

BACKGROUND: In the Fontan palliation for single ventricle heart disease (SVHD), pulmonary blood flow is non-pulsatile/passive, low velocity, and low shear, making viscous power loss a critical determinant of cardiac output. The rheologic properties of blood in SVHD patients are essential for understanding and modulating their limited cardiac output and they have not been systematically studied. We hypothesize that viscosity is decreased in single ventricle circulation. METHODS: We evaluated whole blood viscosity, red blood cell (RBC) aggregation, and RBC deformability to evaluate changes in healthy children and SVHD patients. We altered suspending media to understand cellular and plasma differences contributing to rheologic differences. RESULTS: Whole blood viscosity was similar between SVHD and healthy at their native hematocrits, while viscosity was lower at equivalent hematocrits for SVHD patients. RBC deformability is increased, and RBC aggregation is decreased in SVHD patients. Suspending SVHD RBCs in healthy plasma resulted in increased RBC aggregation and suspending healthy RBCs in SVHD plasma resulted in lower RBC aggregation. CONCLUSIONS: Hematocrit corrected blood viscosity is lower in SVHD vs. healthy due to decreased RBC aggregation and higher RBC deformability, a viscous adaptation of blood in patients whose cardiac output is dependent on minimizing viscous power loss. IMPACT: Patients with single ventricle circulation have decreased red blood cell aggregation and increased red blood cell deformability, both of which result in a decrease in blood viscosity across a large shear rate range. Since the unique Fontan circulation has very low-shear and low velocity flow in the pulmonary arteries, blood viscosity plays an increased role in vascular resistance, therefore this work is the first to describe a novel mechanism to target pulmonary vascular resistance as a modifiable risk factor. This is a novel, modifiable risk factor in this patient population.

Sarcopenia versus clinical frailty scale in predicting the risk of postoperative mortality after emergency laparotomy: a retrospective cohort study.

OBJECTIVES: To compare predictive significance of sarcopenia and clinical frailty scale (CFS) in terms of postoperative mortality in patients undergoing emergency laparotomy METHODS: In compliance with STROCSS statement standards, a retrospective cohort study with prospective data collection approach was conducted. The study period was between January 2017 and January 2022. All adult patients with non-traumatic acute abdominal pathology who underwent emergency laparotomy in our centre were included. The primary outcome was 30-day mortality and secondary outcomes were in-hospital mortality and 90-day mortality. The predictive value of sarcopenia and CFS were compared using the receiver operating characteristic (ROC) curve analysis and multivariable binary logistic regression analysis. RESULTS: A total of 1043 eligible patients were included. The risk of 30-day mortality, in-hospital mortality, and 90-day mortality were 8%, 10%, and 11%, respectively. ROC curve analysis suggested that sarcopenia is a significantly stronger predictor of 30-day mortality (AUC: 0.87 vs. 0.70, P<0.0001), in-hospital mortality (AUC: 0.79 vs. 0.67, P=0.0011), and 90-day mortality (AUC: 0.79 vs. 0.67, P=0.0009) compared with CFS. Moreover, multivariable binary logistic regression analysis identified sarcopenia as an independent predictor of mortality [coefficient: 4.333, OR: 76.16 (95% CI 37.06-156.52), P<0.0001] but not the CFS [coefficient: 0.096, OR: 1.10 (95% CI 0.88-1.38), P=0.4047]. CONCLUSIONS: Sarcopenia is a stronger predictor of postoperative mortality compared with CFS in patients undergoing emergency laparotomy. It cancels out the predictive value of clinical frailty scale in multivariable analyses; hence among the two variables, sarcopenia deserves to be included in preoperative predictive tools.

Low referral rate of overweight/obese patients with hidradenitis suppurativa to weight-management services: a missed opportunity?

Hidradenitis suppurativa (HS) is associated with obesity and other cardiovascular risk factors. Referral of overweight/obese patients with HS to weight-management (WM) services is advised as this may help reduce HS disease severity and cardiovascular risk. A retrospective observational study of 50 patients with HS attending a specialist HS clinic was conducted to assess general practitioner referral patterns of overweight/obese patients with HS for WM. Forty-two patients (84%) were classified as overweight or obese. None of 6 overweight patients and none of 18 obese class 1 patients had been referred to WM prior to dermatology referral, while only 2 of 10 (20%) obese class 2 and 3 of 8 (38%) obese class 3 patients had been referred. The overall WM referral rate for overweight/obese patients was only 12% (n = 5/42). The low referral rate suggests that further efforts are required to diagnose overweight/obesity in primary care, improve the provision of WM services and educate medical professionals that HS is a weight-related comorbidity.

Hearing outcomes following reimplantation of functional legacy cochlear implants.

OBJECTIVES: Recently, patients with certain legacy cochlear implants (CIs) have sought out reimplantation to enjoy the benefits offered by newer processor technology. This decision can be difficult, especially when the individual relies exclusively on the device for communication and scores at the ceiling of performance metrics. To date, most outcome data is derived from reimplantation of a non-functioning CI-a relatively easy decision. The aim of this study is to report hearing outcomes following reimplantation of legacy implants to guide surgeons and patients approaching this high-stakes clinical situation. PATIENTS AND INTERVENTION: Four patients implanted with Advanced Bionics Clarion C1 devices over 20 years ago underwent reimplantation. RESULTS: Three reimplanted patients demonstrated a maintenance or improvement in their audiometric performance with one patient experiencing only a 5 % decrease in AzBioQ score. Each patient expressed satisfaction with the expansion of technological capabilities including improved battery life, and device connectivity. There were no failed reimplantations or other adverse effects. CONCLUSIONS: Reimplantation of a functioning legacy CI result in stability or improvement in auditory performance. All individuals in this series report that they enjoy the new connectivity and programming technologies. As the rate advancement in CI technology continues to increase and newer device architectures emerge, these data will help to inform the decision to reimplant functioning devices.

Staged implantation of active transcutaneous bone conduction hearing devices (BCHD) after explantation of older generation bone anchored hearing aids (BAHAs): Surgical outcomes and approach to management.

PURPOSE: To evaluate outcomes following explantation of percutaneous or transcutaneous bone conduction implants (pBCIs or tBCIs) and subsequent implantation of transcutaneous active bone conduction hearing devices (BCHDs); to provide guidance regarding staging of surgery and adjunctive procedures. MATERIALS AND METHODS: Retrospective chart review of eight adult subjects (ten ears) with pBCIs or tBCIs who underwent explantation of their device and subsequent implantation with a BCHD [MED-EL BONEBRIDGE™ (n = 7, 70 %) or Cochlear™ Osia® (n = 3, 30 %)]. RESULTS: Reasons for pBCI or tBCI explantation were pain (60 %, 6/10), infection (60 %, 6/10), skin overgrowth (50 %, 5/10), and inability to obtain new processors (20 %, 2/10). Median time between pBCI or tBCI removal and BCHD staged implant was 4.7 (IQR 2.2-8.1) months. Two subjects developed complications following BCHD implantation. One had a persistent wound overlying the osseointegrated screw after removal of the pBCI abutment, requiring removal and temporalis rotational flap. Staged Osia® implantation was performed, but ultimately wound dehiscence developed over the device. The second subject experienced an infection after BONEBRIDGE™ implantation (32 days after pBCI explant), necessitating washout and treatment with intravenous antibiotics. There was subsequent device failure. CONCLUSION: The transition from a pBCI or tBCI to a novel transcutaneous device is nuanced. Staged pBCI or tBCI explantation and novel BCHD implantation with sufficient time for wound healing is vital. Adjunctive procedures to augment soft tissue in cases of prior attenuation may be required to avoid complications with larger internal devices.

Patient activation and medication adherence in adults.

BACKGROUND: Patients' level of medication adherence provides conflicting results in its relationship to patient activation. Multiple factors may be contributing to these mixed results. OBJECTIVES: The primary purpose was to assess the association of patient activation to medication adherence in adults with chronic health conditions and low health literacy (HL). Secondary objectives were to determine whether age, education, gender, and race were associated with activation. METHODS: Participants completed self-report questionnaires regarding chronic disease self-management. Patient activation was measured using Hibbard's Patient Activation Measure (PAM). Self-report of medication adherence was determined using the Gonzalez-Lu adherence questionnaire. Block regressions first assessed the relation of demographic variables and education to adherence and then the added relation of patient activation in a second model. RESULTS: The analyses included 301 participants (mean age 58 years; 53% female; mean chronic conditions of 6.6). Some of the most common chronic conditions included hypertension (60%), arthritis (51%), depression (49%), and hyperlipidemia (43%). The relation of older age to greater medication adherence was significant (P < 0.05) in both models. The addition of PAM was significantly related to better adherence (P < 0.001) and also increased the R squared value from 0.04 to 0.09. This change resulted in a moderate effect size (d = 0.50). CONCLUSION: Evaluating patient activation at baseline may predict those more likely to be medication adherent in patients with low HL.

IL-13-associated epithelial remodeling correlates with clinical severity in nasal polyposis.

BACKGROUND: Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes and severity are incompletely described. OBJECTIVE: We sought to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS. METHODS: Using cell-type transcriptional signatures derived from epithelial single-cell sequencing, we analyzed bulk RNA-sequencing data from sinus epithelial brushings obtained from patients with CRS with and without nasal polyps in comparison to healthy controls. RESULTS: The airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, CRS without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell, and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated ("polyp") tuft cell score and a prostaglandin E2 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures. CONCLUSIONS: These results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling.

Cognitive function and impact on driving after SARS-COV-2 infection in a man with long-standing HIV infection: a case report.

A substantial number of individuals who experience COVID-19 infection experience prolonged physical and mental symptoms after resolution of their initial infection, and among them, many individuals experience cognitive difficulties including memory lapses and executive function difficulties, often referred to as "brain fog." The possible impact of COVID-19 infection on cognition in persons with HIV-related cognitive disorders is unknown. In this report, we describe post-COVID-19 cognitive and driving function in a 62-year-old man with HIV infection since the early 1990s.

Identification and characterization of new candidates for abdominal aortic aneurysm screening in patients outside of current accepted guidelines.

BACKGROUND: Previous studies have identified groups of patients with abdominal aortic aneurysm (AAA) that fall outside of currently accepted screening guidelines. Population-based studies have found AAA screening would be cost-effective at a prevalence of 0.5% to 1.0%. The goal of this study was to determine the prevalence of AAA in patients that fall outside of the current screening guidelines. In addition, we analyzed outcomes of the groups with a prevalence of greater than 1%. METHODS: Using the TriNetX Analytics Network, several patient cohorts were abstracted with a diagnosis of ruptured or unruptured AAA based on previously identified groups with a potentially high risk for AAA that fall outside of currently accepted screening guidelines. Groups were also stratified by sex. For groups found to have a prevalence of greater than 1%, the unruptured patients were further analyzed for long-term rates of rupture and included male ever-smokers aged 45 to 65, male never-smokers aged 65 to 75, male never-smokers aged greater than 75, and female ever-smokers aged 65 or greater. Long-term mortality, stroke, and myocardial infarction rates were compared in patients with treated and untreated AAA after propensity score matching. RESULTS: We identified 148,279 patients across the four groups with a prevalence of AAA of greater than 1% with female ever-smokers aged 65 or older being the most prevalent (2.73%). In each of the four groups, the rate of AAA rupture increased every 5 years and all had rupture rates of greater than 1% at 10 years. Meanwhile, controls for each of these four subgroups without a previous AAA diagnosis had rupture rates between 0.090% and 0.013% at 10 years. Those who underwent repair of their AAA had decreased incidence of mortality, stroke, and myocardial infarction. Specifically, male ever-smokers aged 45 to 64 had a significant difference in incidence of mortality and myocardial infarction at 5 years and stroke at 1 and 5 years. CONCLUSIONS: Our analysis suggests male ever-smokers aged 45 to 65, male never-smokers aged 65 to 75, male never-smokers aged greater than 75, and female ever-smokers aged 65 or greater have a more than 1% prevalence of AAA and, therefore, may benefit from screening. Outcomes were significantly worse compared with well-matched controls in these groups.

Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia.

BACKGROUND: Inhaled nitric oxide (iNO) is widely used for the management of infants with congenital diaphragmatic hernia (CDH); however, evidence of benefit is limited. METHODS: This is a multicenter cohort study using data from the Congenital Diaphragmatic Hernia Study Group between 2015 and 2020. The impact of early iNO use in the first 3 days of life prior to ECLS use on mortality or ECLS use was explored using multivariate logistic regression models and subgroup analyses. RESULTS: Of the 1777 infants, 863 (48.6%) infants received early iNO treatment. Infants receiving iNO had lower birth weight, larger defect size, more severe pulmonary hypertension, and abnormal ventricular size and function. After controlling for these factors, early iNO use was associated with increased mortality (aOR 2.06, 95% CI 1.05-4.03, P = 0.03) and increased ECLS use (aOR 3.44, 95% CI 2.11-5.60, P < 0.001). Subgroup analyses after stratification by echocardiographic characteristics and defect size revealed no subgroup with a reduction in mortality or ECLS use. CONCLUSIONS: Use of iNO in the first 3 days of life prior to ECLS was not associated with a reduction in mortality or ECLS use in either the regression models or the subgroup analyses. The widespread use of iNO in this vulnerable population requires reconsideration. IMPACT: Evidence to support widespread use of iNO for infants with congenital diaphragmatic hernia is limited. The use of iNO in the first 3 days of life was associated with significantly increased mortality and ECLS use. Stratification by echocardiographic characteristics and defect size did not reveal a subgroup that benefited from iNO. Even the subset of patients with R-to-L shunts at both ductal and atrial levels, a surrogate for elevated pulmonary arterial pressures in the absence of significantly decreased LV compliance, did not benefit from early iNO use. Early iNO therapy was of no benefit in the management of acute pulmonary hypertension in infants with congenital diaphragmatic hernia, supporting reconsideration of its use in this population.

VITRECTOMY FOR VITREOUS HEMORRHAGE ASSOCIATED WITH RETINAL VEIN OCCLUSION: Visual Outcomes, Prognostic Factors, and Sequelae.

PURPOSE: To report the outcomes of pars plana vitrectomy for vitreous hemorrhage (VH) associated with retinal vein occlusion and to identify prognostic indicators. METHODS: Interventional, retrospective consecutive case series between 2015 and 2021. RESULTS: The study included 138 eyes of 138 patients (64 female and 74 male); 81 patients had branch retinal vein occlusion and 57 had central retinal vein occlusion. The mean age was 69.8 years. The mean duration between the diagnosis of VH and surgery was 79.6 ± 115.3 (range, 1-572) days. The mean follow-up was 27.2 months. The logarithm of the minimum angle of resolution visual acuity significantly improved from 1.95 ± 0.72 (Snellen equivalent, 20/1782) to 0.99 ± 0.87 (20/195) at 6 months and to 1.06 ± 0.96 (20/230) at the final visit (both P < 0.001). The visual acuity at 6 months improved by three or more lines in 103 eyes (75%). Postoperative complications during follow-up included recurrent VH in 16 eyes (12%) (of which 8 eyes underwent reoperations), rhegmatogenous retinal detachment in six eyes (4%), and new neovascular glaucoma in three eyes (2%). Worse final visual acuity was significantly associated with older age ( P = 0.007), concurrent neovascular glaucoma ( P < 0.001), central retinal vein occlusion ( P < 0.001), worse preoperative visual acuity ( P < 0.001), postoperative new neovascular glaucoma ( P = 0.021), and postoperative retinal detachment ( P < 0.001). The duration of VH was not associated with visual outcomes ( P = 0.684). Preoperative antivascular endothelial growth factor injections and tamponade did not prevent postoperative recurrent VH. CONCLUSION: Pars plana vitrectomy is effective for VH associated with retinal vein occlusion, regardless of the duration of hemorrhage. However, pre-existing risk factors and postoperative sequelae may limit visual recovery.

Opportunities for implementing a patient-initiated follow-up pathway for patients with psoriasis completing phototherapy.

We performed a retrospective case analysis to identify opportunities to introduce a patient-initiated follow-up (PIFU) pathway for patients with psoriasis completing narrowband ultraviolet B phototherapy at our centre. In total, 42 patients completed phototherapy between January 2016 and August 2018 and outcomes were observed for 36 months after phototherapy cessation. Had a PIFU pathway been in place, 24 routine follow-up appointments could have been saved and 8 nonattendances could have been avoided. Seven patients who were discharged or did not attend follow-up after phototherapy flared within 12 months and could have benefited from PIFU to re-access dermatology care. In total 21 patients (50.0%) experienced a relapse within 36 months of completion of phototherapy, and 18 of these (85.7%) relapsed at 0-12 months. The median time to relapse was 6 months. We conclude a post-phototherapy PIFU pathway could help eliminate unnecessary appointments for patients in remission and improve access for patients who relapse. A 12-month PIFU duration prior to discharge would be sufficient to capture the majority of relapses.

Ancillary techniques to improve dermoscopy specificity for skin cancer detection.

Although the use of dermoscopy has markedly improved both the sensitivity and specificity for skin cancer detection, there is still opportunity for improvement. Ancillary techniques provide additional ways to assess a lesion with the aim of improving our diagnostic ability with little extra cost. Usage of these techniques can strengthen diagnosis and help reduce unnecessary biopsies of benign lesions.

Safety of Continuing Anticoagulation Prior to Cardiac Catheterization in Pediatric Patients: A Los Angeles Center Experience.

This is the first report specifically describing outcomes of pediatric patients who underwent cardiac catheterization while on uninterrupted anticoagulation. One hundred forty-four cardiac catheterizations were identified that met inclusion criteria at our institution from 11/2014 to 10/2019. The median age and weight of the patients were 6.3 [0.01-20.9] years and 19.3 [2.1-172.5] kg, respectively. Seventy-eight (54%) catheterizations involved inpatients. The most common cardiac diagnoses among the cohort were single ventricle (n = 41), conotruncal defects (n = 37), and structurally normal heart (n = 16). The most common indications for anticoagulation were arterial/venous thrombus (n = 45), Fontan physiology (n = 32), and mechanical valve thrombus prophylaxis (n = 27). The anticoagulation medications used were warfarin (n = 57), heparin (n = 52), enoxaparin (n = 25), fondaparinux (n = 5), rivaroxaban (n = 2), and both heparin and warfarin (n = 3). Interventions were performed in 96 cases (67%). The median length of the procedure was 122.5 [15-760] minutes, and the median time to achieve hemostasis was 18.0 [range: 5-76, IQR: 13-25] minutes. Adverse events were present in 11 cases (7.6%), and of those only 2 cases (1.4%) were bleeding-related complications. Our single-center data suggest that performing cardiac catheterization on pediatric patients while on uninterrupted anticoagulation is safe and does not substantially increase the risk of bleeding complications based on a cohort of patients that varied in age, size, diagnosis, medical complexity, and type of intervention performed. Patients on warfarin therapy for a mechanical valve are most likely to benefit from this practice, as the ability to continue warfarin therapy avoids the need for bridging and other interruption-related complications.

"Heart of the Matter": Cardiac Dysfunction in Congenital Diaphragmatic Hernia.

Despite advances in caring for neonates with congenital diaphragmatic hernia (CDH), mortality and morbidity continues to be high. Additionally, the pathophysiology of cardiac dysfunction in this condition is poorly understood. Postnatal cardiac dysfunction in neonates with CDH may be multifactorial with origins in fetal life. Mechanical obstruction, competition from herniated abdominal organs into thoracic cavity combined with redirection of ductus venosus flow away from patent foramen ovale leading to smaller left-sided structures may be a contributing factor. This shunting decreases left atrial and left ventricular blood volume, which may result in altered micro- and macrovascular aberrations affecting cardiac development in the prenatal period. Direct mass effect from herniated intra-abdominal contents restricting cardiac growth and/or reduced left ventricular preload may contribute independently to left ventricular dysfunction in the absence of right ventricular dysfunction and or pulmonary hypertension. With variable clinical phenotypes of cardiac dysfunction, pulmonary hypertension, and respiratory failure in patients with CDH, there is increased need for individualized diagnosis and tailored therapy. Routine use of therapy such as inhaled nitric oxide and sildenafil that induces significant pulmonary vasodilation may be detrimental in left ventricle dysfunction, whereas in a patient with pure right ventricle dysfunction, they may be beneficial. Targeted functional echocardiography serves as a real-time tool for defining the pathophysiology and aids optimization of vasoactive therapy in affected neonates. KEY POINTS: · Cardiac dysfunction in neonates with CDH is multifactorial.. · Postnatal cardiac dysfunction in patients with CDH has its origins in fetal life.. · Right ventricular dysfunction contributes to systemic hypotension.. · Left ventricular dysfunction contributes to systemic hypotension.. · Supportive therapy should be tailored to clinical phenotype..

Disease recidivism after subtotal petrosectomy and ear canal closure.

PURPOSE: To describe the presentation, diagnosis, and management of chronic otitis media recidivism after subtotal petrosectomy and ear canal closure (STP). MATERIALS AND METHODS: Patients with temporal bone pathology detected during follow-up after STP were identified in the electronic medical record. Pertinent clinical details regarding surveillance plan, presentation, imaging findings, and revision surgery were collected and analyzed. RESULTS: A total of 10 patients were identified with recurrent or persistent pathology after STP. The median time to detection was 46 months (IQR 24-84). Five patients (50 %) had non-specific symptomatology, 4 patients (40 %) were completely asymptomatic, and 1 patient (10 %) was asymptomatic outside of two instances of mastoiditis with cochlear implant device infection treated with incision and drainage. One patient (10 %) was noted to have proptosis on examination, but no other patients had objective signs of disease at detection of disease recidivism. Nine (90 %) patients had pathology identified on preoperative imaging. All patients underwent revision surgery, with identification of cholesteatoma in 8 cases (80 %) and cholesterol granuloma in 2 cases (20 %). Extensive disease was noted in 6 patients (60 %), all of whom followed-up greater than 3 years from surgery. All patients tolerated revision surgery without complication. CONCLUSIONS: Recidivistic disease often remains clinically silent for extended periods of time after STP. Planned follow-up - with imaging or second look surgery - to facilitate early detection should be considered. Undetected disease recurrence or development may result in morbidity in a proportion of patients if surveillance is not performed.

Role of microRNAs in Congenital Diaphragmatic Hernia-Associated Pulmonary Hypertension.

Epigenetic regulators such as microRNAs (miRNAs) have a key role in modulating several gene expression pathways and have a role both in lung development and function. One of the main pathogenetic determinants in patients with congenital diaphragmatic hernia (CDH) is pulmonary hypertension (PH), which is directly related to smaller lung size and pulmonary microarchitecture alterations. The aim of this review is to highlight the importance of miRNAs in CDH-related PH and to summarize the results covering this topic in animal and human CDH studies. The focus on epigenetic modulators of CDH-PH offers the opportunity to develop innovative diagnostic tools and novel treatment modalities, and provides a great potential to increase researchers' understanding of the pathophysiology of CDH.