Incidental Renal Cysts Found by Point-of-Care Ultrasound: A Retrospective Chart Review.

BACKGROUND: Incidental findings are unrelated to a patient's complaint, found on diagnostic imaging, such as point-of-care ultrasound (POCUS). Incidental findings represent potential harms to patients and may lead to increased patient anxiety and health care costs related to downstream testing and surveillance. STUDY OBJECTIVES: In this study, we aimed to calculate the rate of incidental renal cysts found by POCUS. Further, we hoped to describe how emergency physicians relay the findings to patients. Lastly, we hoped to examine if patients suffered harms in the 12 months following identification of an incidental renal cyst. METHODS: From our single-center, academic emergency department (ED), we reviewed renal POCUS images from 1000 consecutive adult ED patients to determine if there was a renal cyst. Next, we performed manual chart review to determine if patients were informed of the incidental renal cyst or suffered any patient harms. RESULTS: We found the prevalence of renal cysts to be 6.5% (95% confidence interval: 4.9%-8.4%). Those with cysts were more likely to be older compared to those without (63 ± 14 vs. 49 ± 15 years of age). Only 8% of patients had evidence that they were informed of their incidental renal cyst. No patients received a biopsy or were diagnosed with renal cell carcinoma or polycystic kidney disease. CONCLUSION: Incidental renal cysts are common and are more likely to be found in older adults. In our study, physicians infrequently informed patients of their incidental finding.

Retrograde Flow of Fluid Through the Nasolacrimal Duct System Under General Anesthesia: A Case Report.

This case report describes a rare incident of fluid exhibiting retrograde flow from the nasopharynx through the nasolacrimal duct and accumulating within the eye guard while under general anesthesia. The patient was in a steep Trendelenburg position for several hours and received multiple liters of intravenous fluid. The patient did not have a history of sinusitis, sinus surgery, cocaine use, dacryostenosis and dacryocystitis, or nasolacrimal duct irrigation and probing. This case provides insight into the potential ophthalmic implications of surgical and anesthetic management. While the patient fortunately had no complications, this case also underscores the importance of intraoperative vigilance.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Applications of Human Pluripotent Stem Cell-Derived Skin Organoids in Dermatology.

Pluripotent stem cells have the potential to become any cell type, and recently, they have been used to create organoids that can recapitulate several pertinent features of human organs. Skin organoids have been developed that possess many of the crucial accessory organs, including hair follicles, sebaceous glands, nerves, fat, and melanocytes. These skin organoids present the opportunity to study skin development and disease as well as perform screens to identify new drug candidates. In the future, skin organoids might augment clinical practice by serving as source material for transplantation to treat wounds or other conditions. Nevertheless, several limitations, such as the lengthy differentiation protocol, which can result in heterogeneous products, must first be addressed before the full potential of skin organoids can be realized. The purpose of this article is to provide a broad overview of skin organoids so that a broader audience can become familiar with this technology, which has important implications for dermatologic research and medicine.

Factors associated with long-term outcomes of CD19 CAR T-cell therapy for relapsed/refractory CLL.

High response rates have been reported after CD19-targeted chimeric antigen receptor-modified (CD19 CAR) T-cell therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), yet the factors associated with duration of response in this setting are poorly characterized. We analyzed long-term outcomes in 47 patients with R/R CLL and/or Richter transformation treated on our phase 1/2 clinical trial of CD19 CAR T-cell therapy with an updated median follow-up of 79.6 months. Median progression-free survival (PFS) was 8.9 months, and the 6-year PFS was 17.8%. Maximum standardized uptake value (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.07-1.23; P < .001) and bulky disease (≥5 cm; HR, 2.12; 95% CI, 1.06-4.26; P = .034) before lymphodepletion were associated with shorter PFS. Day +28 complete response by positron emission tomography-computed tomography (HR, 0.13; 95% CI, 0.04-0.40; P < .001), day +28 measurable residual disease (MRD) negativity by multiparameter flow cytometry (HR, 0.08; 95% CI, 0.03-0.22; P < .001), day +28 MRD negativity by next-generation sequencing (HR, 0.21; 95% CI, 0.08-0.51; P < .001), higher peak CD8+ CAR T-cell expansion (HR, 0.49; 95% CI; 0.36-0.68; P < .001), higher peak CD4+ CAR T-cell expansion (HR, 0.47; 95% CI; 0.33-0.69; P < .001), and longer CAR T-cell persistence (HR, 0.56; 95% CI, 0.44-0.72; P < .001) were associated with longer PFS. The 6-year duration of response and overall survival were 26.4% and 31.2%, respectively. CD19 CAR T-cell therapy achieved durable responses with curative potential in a subset of patients with R/R CLL. This trial was registered at www.clinicaltrials.gov as #NCT01865617.

Warts in pediatric oncology patients: A single-institution retrospective study.

BACKGROUND: Pediatric oncology patients undergoing cancer treatment can often have numerous and recalcitrant cutaneous warts due to their underlying immunosuppression. There are little published data on the optimal management of warts in pediatric oncology patients undergoing active cancer treatment compared to patients having completed treatment. Our objective was to analyze the clinical course of warts treated within this patient population at Boston Children's Hospital over a 10-year period. METHODS: This was a single-institution retrospective study of 72 pediatric oncology patients from 1 September 2011 to 1 September 2021 who were treated for warts at Boston Children's Hospital. All patients had a diagnosis of cutaneous warts with at least one follow-up visit and were receiving active treatment for cancer either during or after concurrent treatment of their warts. We examined the modality and effectiveness of wart treatments while both on and offactive treatment of their cancer. RESULTS: The median age was 12 years (range 4-18). Fifty-four percent of patients were documented to have plantar warts. Sixty percent of patients with a documented number of warts had more than five warts at presentation. For cases in which outcomes were specified, treatment resulted in complete resolution of warts in only 24.0% of patients undergoing active cancer treatment compared to 63.3% of patients not on active treatment. Warts persisted or worsened in 56.0% of patients undergoing active cancer treatment compared to only 13.4% of patients not on active treatment. CONCLUSION: These data may help guide clinicians in evaluating and treating warts in pediatric oncology patients.

Systematic Approach to Pediatric Macrocephaly.

Macrocephaly, defined as a head circumference greater than 2 standard deviations above the mean, is a relatively common presenting symptom in the pediatric population at routine well-child examinations and a common indication for neuroimaging. Multiple imaging modalities are complementary in evaluating macrocephaly, including US, CT, and MRI. The differential diagnosis for macrocephaly is broad, and many disease processes lead to macrocephaly only when the sutures are open. In patients with closed sutures, these entities instead lead to increased intracranial pressure, according to the Monroe-Kellie hypothesis, which states that there is an equilibrium between intracranial constituents due to the fixed intracranial volume. The authors describe a useful paradigm for classifying macrocephaly by identifying which of the four components of the cranium (ie, cerebrospinal fluid, blood and vasculature, brain parenchyma, or calvarium) has an increased volume. Patient age, additional imaging findings, and clinical symptoms are also useful features. Most cases in the pediatric population are due to increased cerebrospinal fluid spaces, such as benign enlargement of the subarachnoid space, which must be carefully distinguished from subdural fluid collections in patients with accidental or nonaccidental trauma. Other common causes of macrocephaly are discussed, including hydrocephalus secondary to an aqueductal web, hemorrhage, or a neoplasm. The authors also provide information on some of the rarer diseases for which imaging may provide the impetus for genetic testing (eg, overgrowth syndromes and metabolic disorders). ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Role of Tumor Necrosis Factor-α Inhibitors in the Treatment and Occurrence of Acne: A Systematic Review.

Importance: Tumor necrosis factor-α inhibitors (TNFis) approved to treat several inflammatory diseases are sometimes used off label to treat severe forms of acne that are refractory to conventional therapies. However, use of TNFis can also be followed by acne occurrence, suggesting an association between TNFis and acne. Most of the literature on the topic comprises case reports and series that have not been reviewed in a systematic manner. Objective: To characterize the demographic characteristics, clinical presentations, treatments, and outcomes of patients receiving TNFis to treat acne and patients who develop acne following treatment of other conditions with TNFis. Evidence Review: A systematic literature review was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. PubMed and Web of Science were searched from inception through October 17, 2022. Included studies reported on patients of any sex or age who received TNFis whose treatment was followed by resolution or occurrence of acne. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. Findings: A total of 53 studies reporting on 64 patients who received TNFis for the treatment of acne (n = 47) or who experienced acne after treatment with TNFis for a different condition (n = 17) (mean age, 28.7 years; range, 12-64 years; 6 female individuals [8.8%]) were included. The TNFis used included adalimumab, infliximab, and etanercept. Among the 47 patients treated for acne with TNFis, most had previously received antibiotics (31 [66.0%]) or isotretinoin (32 [68.1%]). Most (44 [93.6%]) experienced partial improvement (25 [53.2%]) or clearance (19 [40.4%]) with very few adverse effects reported (3 [6.4%]). Acne manifested as part of an inflammatory syndrome for 30 patients (63.8%). Among the 17 patients treated TNFis for a different condition followed by the occurrence of acne, only 1 patient (5.9%) reported having a history of acne. Therapy with TNFis was either discontinued (8 [47.1%]) or altered (6 [35.3%]) in most patients due to acne occurrence, typically with improvement in symptoms. Conclusions and Relevance: The results of this systematic review suggest that TNFis can be effective in treating refractory acne but can also be associated with the occurrence of acne in certain instances. Further studies elucidating the role that TNF plays in treating and inducing acne could yield insight into off-label TNFi use and acne pathogenesis, potentially guiding clinical care of patients with acne treated or induced by TNFis.

Pearls and updates: cutaneous signs of systemic malignancy.

PURPOSE OF REVIEW: Children with systemic malignancies can present with concomitant dermatological manifestations. Cutaneous findings can occur before, during or after diagnosis. Recognizing these features can aid in diagnosis, inform prognosis, and help determine appropriate treatment. Following a review of the literature published over the past two years, we provide an update on cutaneous signs of pediatric systemic malignancies, concentrating on; leukemia cutis, lymphoma cutis, neuroblastoma, sarcomas, Langerhans cell histiocytosis and paraneoplastic syndromes. RECENT FINDINGS: Authors highlight the persistently heterogeneous features of cutaneous manifestations of systemic malignancy. Findings are often nonspecific, and a definitive diagnosis requires skin biopsy with immunophenotyping. Several studies describe dermoscopy features, demonstrating this as a useful tool in clinical evaluation. Genetic mutations underlying the pathogenesis of disease continue to be elucidated. Further, advances in medical treatment led to improved prognosis in many systemic malignancies, with early and aggressive treatment heralding better outcomes. SUMMARY: Comprehensive cutaneous evaluation alongside thorough clinical history and review of systems remains of paramount importance as dermatological manifestations of systemic malignancy are notoriously variable with a shared feature of often appearing benign but persisting despite usual treatment. Urgent referral to dermatology is recommended when suspicion for any cutaneous presentation of malignancy arises.

Expectant Management of Blunt Grade III Renal Injuries: Early Discharge Outcomes From a Level I Trauma Center.

OBJECTIVES: To determine whether patients with American Association for the Surgery of Trauma (AAST) grade III blunt renal injuries discharged within 48 hours of admission have increased rates of readmission for renal-related complications compared to patients observed for over 48 hours. METHODS: Renal trauma patients from 2005 through 2020 were identified from our institutional trauma registry. Patients with AAST III blunt renal injuries who survived beyond 48 hours of admission were included. Univariable analysis was used to identify variables associated with discharge within 48 hours. Reasons for readmission were compared between patients discharged before and after 48 hours of admission. RESULTS: Of the 1751 renal trauma patients, 377 (21.5%) met inclusion criteria. Sixty-five of 377 (17.2%) AAST III injuries were discharged within 48 hours of admission. Forty (10.6%) patients required readmission, 3 in the early discharge group and 37 in the standard discharge group. No patient required readmission for renal-related complications. CONCLUSION: Patients with AAST grade III blunt renal injuries are not at increased risk for early renal-related complications if discharged within 48 hours of admission and should be considered for early discharge. The very low rate of renal-related complications for AAST III blunt renal injuries supports their categorization as "low-grade" renal trauma.

Toxic epidermal necrolysis-like acute graft-versus-host disease in pediatric bone marrow transplant patients: Case series and review of the literature.

BACKGROUND/OBJECTIVES: Complications of hematopoietic stem cell transplant (HSCT) include acute graft-versus-host disease (aGVHD). Severe cutaneous aGVHD can present with generalized erythroderma, desquamation, and bullae which can mimic toxic epidermal necrolysis (TEN). TEN occurs in response to a culprit medication. Transplant patients are often on many medications, making it difficult to distinguish between the two conditions. Given that TEN-like aGVHD is rare, we describe a case series of pediatric patients and review the literature. METHODS: This is a multi-institutional case series of children who developed TEN-like aGVHD following bone marrow transplantation. Demographic, clinical, and treatment information was collected. RESULTS: Ten patients were identified. Median age at transplantation was 8.5 years (range 0.12-17 years). Median time from transplant to first skin symptoms was 35 days (range 6-110 days) and to first TEN-like symptoms was 40 days (range 16-116 days). 7/10 had other organ GVHD involvement. All patients were on concurrent medications at time of first skin symptoms including immunosuppression for GVHD prophylaxis, infection prophylaxis or treatment, and pain medication. Treatments for TEN-like aGVHD included immunosuppression. CONCLUSIONS: We observe that patients with > or equal to 50% BSA involvement of their skin with TEN-like aGVHD, extracutaneous GVHD, and lack of reepithelization tend to have poor outcomes. Given the rarity of this condition, multidisciplinary care of these patients is important for accurate and timely diagnosis and treatment.

Supportive Oncodermatology in Pediatric Patients.

Cutaneous reactions to targeted therapies are varied and common. Pediatric dermatology literature is emerging on the specific types and prevalence of cutaneous reactions to targeted therapies that hone in on membrane-bound receptors, intracellular signaling targets, and antiangiogenesis agents, as well as targeted immunotherapies. Data regarding the timing, severity, and treatment algorithms are most plentiful for BRAF, MEK, and EGFR inhibitors.

Sirt3 Pharmacologically Promotes Insulin Sensitivity through PI3/AKT/mTOR and Their Downstream Pathway in Adipocytes.

Sirtuin-3 (Sirt3) is a major mitochondrial deacetylase enzyme that regulates multiple metabolic pathways, and its expression is decreased in diabetes type 1 and type 2 diabetes. This study aimed to elucidate Sirt3's molecular mechanism in regulating insulin sensitivity in adipocytes that can contribute to the effort of targeting Sirt3 for the treatment of obesity and type 2 diabetes. We found that the Sirt3 activator honokiol (HNK) induced adipogenesis compared to the control, in contrast to Sirt3 inhibitor, 3-TYP. Accordingly, HNK increased expression of adipocyte gene markers, gene-involved lipolysis and glucose transport (GLUT4), while 3-TYP reduced expression of those genes. Interestingly, 3-TYP caused an increase in gene expression of adipocyte-specific cytokines including IL6, resistin, and TNF-α. However, changes in adipocyte-specific cytokines in HNK treated cells were not significant. In addition, HNK stimulated insulin pathway by promoting insulin receptor beta (IRß) and PI3K/AKT/mTOR pathways, resulting in an increase in phosphorylation of the forkhead family FoxO1/FoxO3a/FoxO4 and glycogen synthase kinase-3 (GSK-3ß), opposing 3-TYP. In line with these findings, HNK increased free fatty acid and glucose uptake, contrary to 3-TYP. In conclusion, Sirt3 activator-HNK induced adipogenesis and lipolysis reduced adipocytes specific cytokines. Intriguingly, HNK activated insulin signaling pathway and increased free fatty acid as well as glucose uptake and transport, in sharp contrast to 3-TYP. These results indicate that, via insulin signaling regulation, Sirt3 activation by HNK improves insulin resistance, while Sirt3 inhibition by 3-TYP might precipitate insulin resistance.

Variability in personal protective equipment in cross-sectional interventional abdominal radiology practices.

PURPOSE: To determine institutional practice requirements for personal protective equipment (PPE) in cross-sectional interventional radiology (CSIR) procedures among a variety of radiology practices in the USA and Canada. METHODS: Members of the Society of Abdominal Radiology (SAR) CSIR Emerging Technology Commission (ETC) were sent an eight-question survey about what PPE they were required to use during common CSIR procedures: paracentesis, thoracentesis, thyroid fine needle aspiration (FNA), superficial lymph node biopsy, deep lymph node biopsy, solid organ biopsy, and ablation. Types of PPE evaluated were sterile gloves, surgical masks, gowns, surgical hats, eye shields, foot covers, and scrubs. RESULTS: 26/38 surveys were completed by respondents at 20/22 (91%) institutions. The most common PPE was sterile gloves, required by 20/20 (100%) institutions for every procedure. The second most common PPE was masks, required by 14/20 (70%) institutions for superficial and deep procedures and 12/12 (100%) institutions for ablation. Scrubs, sterile gowns, eye shields, and surgical hats were required at nearly all institutions for ablation, whereas approximately half of institutions required their use for deep lymph node and solid organ biopsy. Compared with other types of PPE, required mask and eye shield use showed the greatest increase during the SARS-CoV-2 pandemic. CONCLUSION: PPE use during common cross-sectional procedures is widely variable. Given the environmental and financial impact and lack of consensus practice, further studies examining the appropriate level of PPE are needed.

Fetal counseling for congenital heart disease: is communication effective?

PURPOSE: To assess the accuracy of maternal understanding of fetal cardiac defects following initial fetal counseling. METHODS: Pregnant women with a fetal diagnosis of congenital heart disease (CHD) were surveyed regarding understanding of their fetus's heart defect. The survey asked: (1) for a description of the heart condition; (2) how confident they were in the diagnosis; (3) whether their fetus would require heart surgery. Two fetal cardiologists evaluated the maternal qualitative description. Partners were excluded from the study. RESULTS: Fifty-one participants consented and 39 completed the survey. Mean age was 31 years, 60% had some college level or post-graduate education, 48% had Medicaid insurance, and 81% were Caucasian. More than three-quarters of participants, stated they had either "quite a bit" or "very much" understanding of their fetus's diagnosis. Maternal assessment matched the physician's assessment of accuracy with 77% (N = 30) demonstrating either "quite a bit" or a "very accurate" description of the diagnosis. All women correctly understood if their fetus would require heart surgery. Highest level of maternal education positively correlated with the accuracy of diagnosis (regression coefficient 0.48, p < .002). However, confidence in the diagnosis was independent of both education (0.30, p = .167) and maternal age (-0.03, p = .234). CONCLUSIONS: Fetal counseling is effective in conveying anatomy and the need for surgery; however, accuracy amongst women with lower levels of education and maternal confidence in understanding can be improved.

Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps. Here, we found distinct microbial signatures between patients with and without polyps and between polyp subtypes using sequencing and culturing techniques. We found a correlation between Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp. Additional analysis revealed that B. fragilis from patients with polyps are bft-negative, activate NF-κB through Toll-like receptor 4, induce a pro-inflammatory response, and are enriched in genes associated with LPS biosynthesis. This study provides fundamental insight into the microbial microenvironment of the pre-neoplastic polyp by highlighting strain-specific genomic and proteomic differences, as well as more broad compositional differences in the microbiome.

Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder.

Diabetes mellitus (DM) is the leading cause of chronic kidney disease and diabetic nephropathy is widely studied. In contrast, the pathobiology of diabetic urinary bladder disease is less understood despite dysfunctional voiding being common in DM. We hypothesised that diabetic cystopathy has a characteristic molecular signature. We therefore studied bladders of hyperglycaemic and polyuric rats with streptozotocin (STZ)-induced DM. Sixteen weeks after induction of DM, as assessed by RNA arrays, wide-ranging changes of gene expression occurred in DM bladders over and above those induced in bladders of non-hyperglycaemic rats with sucrose-induced polyuria. The altered transcripts included those coding for extracellular matrix regulators and neural molecules. Changes in key genes deregulated in DM rat bladders were also detected in db/db mouse bladders. In DM rat bladders there was reduced birefringent collagen between detrusor muscle bundles, and atomic force microscopy showed a significant reduction in tissue stiffness; neither change was found in bladders of sucrose-treated rats. Thus, altered extracellular matrix with reduced tissue rigidity may contribute to voiding dysfunction in people with long-term DM. These results serve as an informative stepping stone towards understanding the complex pathobiology of diabetic cystopathy.

The Impact of Delayed-Phase Imaging at Admission on the Management of Urinary Extravasation in High-Grade Renal Trauma.

PURPOSE: American Urological Association Urotrauma guidelines recommend delayed-phase imaging on presentation for all renal injuries, although data to support it are anecdotal. Forgoing delays risks unrecognized collecting system injuries. We hypothesized that renal trauma patients without admission delays have more complications from urinary extravasation. MATERIALS AND METHODS: From 2005 through 2020, 1,751 renal trauma patients were identified from our institutional trauma registry. Included patients had an estimated American Association for the Surgery of Trauma renal injury grade of III-V and a perinephric fluid collection. Propensity scores for receipt of delayed-phase imaging were calculated based on Injury Severity Score, arrival condition, admission systolic blood pressure, sex and renal injury grade. Propensity score-adjusted logistic regression was used to compare clinical outcomes between those with and without admission delays. RESULTS: Ninety (28.6%) of 315 included patients had delays on presentation. Patients without delays had higher Injury Severity Scores (29 vs 23, p=0.002), fewer isolated renal injuries (27.6% vs 38.9%, p=0.05) and lower grade renal injuries (56.9% vs 41.1% grade 3, p=0.03). After propensity score adjustment, patients with delays were more likely to undergo immediate interventions (OR 11.75, 95% CI 2.99-78.10) and interval stent placement for urinary extravasation (OR 6.86, 95% CI 1.56-47.64) without a difference in urological complications (OR 5.07, 95% CI 0.25-766.16). CONCLUSIONS: Delayed-phase imaging was associated with an increased odds of undergoing immediate and asymptomatic interval urological interventions without a difference in the odds of a complication after high-grade renal trauma. Post-trauma urinary extravasation requires further research to determine which patients require imaging and intervention.