Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma.

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour. We generated whole-genome methylation data using the Illumina EPIC microarray in a novel PT cohort (n = 33) and curated methylation microarray data from published datasets including PTs and other potentially histopathologically similar tumours (total n = 817 samples). Analyses revealed that PTs have a unique methylome compared to normal breast tissue and to potentially histopathologically similar tumours (metaplastic breast cancer, fibroadenoma and sarcomas), with PT-specific methylation changes enriched in gene sets involved in KRAS signalling and epithelial-mesenchymal transition. Next, we identified 53 differentially methylated regions (DMRs) (false discovery rate < 0.05) that specifically delineated malignant from non-malignant PTs. The top DMR in both discovery and validation cohorts was hypermethylation at the HSD17B8 CpG island promoter. Matched PT single-cell expression data showed that HSD17B8 had minimal expression in fibroblast (putative tumour) cells. Finally, we created a methylation classifier to distinguish PTs from metaplastic breast cancer samples, where we revealed a likely misdiagnosis for two TCGA metaplastic breast cancer samples. In conclusion, DNA methylation alterations are associated with PT histopathology and hold the potential to improve our understanding of PT molecular aetiology, diagnostics, and risk stratification. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Cost-Effectiveness of Radar Localisation Versus Wire Localisation for Wide Local Excision of Non-palpable Breast Cancer.

BACKGROUND: Wire localisation (WL) is the "gold standard" localisation technique for wide local excision (WLE) of non-palpable breast lesions but has disadvantages that have led to the development of wireless techniques. This study compared the cost-effectiveness of radar localisation (RL) to WL. METHODS: This was a single-institution study of 110 prospective patients with early-stage breast cancer undergoing WLE using RL with the SCOUT® Surgical Guidance System (2021-2023) compared with a cohort of 110 patients using WL. Margin status, re-excision rates, and surgery delays associated with preoperative localisation were compared. Costs from a third-party payer perspective in Australian dollars (AUD$) calculated by using microcosting, break-even point, and cost-utility analyses. RESULTS: A total of 110 WLEs using RL cost a total of AUD$402,281, in addition to the device cost of AUD$77,150. The average additional cost of a surgery delay was AUD$2318. Use of RL reduced the surgery delay rate by 10% (p = 0.029), preventing 11 delays with cost savings of AUD$25,496. No differences were identified in positive margin rates (RL: 11.8% vs. WL: 17.3%, p = 0.25) or re-excision rates (RL: 14.5% vs. WL: 21.8%, p = 0.221). In total, 290 RL cases are needed to break even. The cost of WLE using RL was greater than WL by AUD$567. There was a greater clinical benefit of 1.15 quality-adjusted life-years (QALYs) and an incremental cost-utility ratio of AUD$493 per QALY favouring RL. CONCLUSIONS: Routine use of RL was a more cost-effective intervention than WL. Close to 300 RL cases are likely needed to be performed to recover costs of the medical device. CLINICAL TRIAL REGISTRATION: ACTRN12624000068561.

Substantiating and Adopting Lung Ultrasound Scores to Predict Surfactant Need in Preterm Neonates with Respiratory Distress Syndrome within an Institution.

OBJECTIVE: Administering surfactant timely and appropriately is important to minimize lung injury but remains challenging in preterm neonates with respiratory distress syndrome. The published literature supports that lung ultrasound (LUS) score can predict surfactant need. Neonatal LUS scanning specification and parameter setting guidelines have been recently published for standardization. However, variations in scanning protocols and machine settings hinder its clinical implementation widely. This observational study aims to internally validate the suggested LUS protocol in a neonatal intensive care unit to establish a correlation between LUS scores and surfactant need as the first step of integrating LUS in the clinical practice. STUDY DESIGN: LUS was performed on 40 eligible preterm neonates within 3 hours after birth or before surfactant administration between May 2020 and March 2021. The neonates were between 27 and 32 weeks' gestational age, and all had respiratory distress. Neonates with known congenital anomalies were excluded. A high-frequency linear probe was used to obtain LUS images from six lung zones which were scored using a 0 to 3 system, yielding a maximum of 18 points. Treating physicians were blinded to the LUS score. Receiver operating characteristic analysis determined the optimal LUS score cutoff for predicting surfactant need. RESULTS: Fifteen of the 40 neonates (38%) required higher oxygen fraction and received surfactant. In our cohort, an LUS score ≥10 was identified as the optimal cutoff for predicting surfactant need, with a sensitivity of 80% and specificity of 84%. The area under the curve was 0.8 (p = 0.0003). LUS predicted surfactant need at a median of 3.5 hours earlier than traditional clinical decision (p < 0.0037). CONCLUSION: LUS is a helpful adjunct for predicting surfactant need in preterm neonates. This study describes an approach to implement the LUS protocol and score for clinical decision-making in the clinical practice. KEY POINTS: · LUS is a helpful adjunct for predicting surfactant need in preterm neonates.. · Machine setting variation and probe selection may affect LUS image and score.. · LUS score should be validated at the local unit before clinical implementation..

Essentials of Point-of-Care Ultrasound Coding and Billing at the Neonatal Intensive Care Unit Setting in the United States.

Point-of-care ultrasound (POCUS) has increasingly been used by neonatal providers in neonatal intensive care units in the United States. However, there is a lack of literature addressing the complexities of POCUS coding and billing practices in the United States. This article describes the coding terminology and billing process especially those relevant to neonatal POCUS. We elucidate considerations for neonatal POCUS billing framework and workflow integration. Directions on image storage and supporting documentation to facilitate efficient reimbursement, compliance with billing regulations, and appeal to insurance claim denial are discussed. KEY POINTS: · Code neonatal POCUS procedure precisely allows accurate reimbursement and reduced errors in billing.. · Document details to support medical necessity and reimbursement claims effectively.. · Adhere to regulations to avoid audits, denials, and ensure proper reimbursement..

Unveiling pseudo-pulseless electrical activity (pseudo-PEA) in ultrasound-integrated infant resuscitation.

Point-of-care ultrasound (POCUS) holds immense potential to manage critically deteriorating infants within the neonatal intensive care unit (NICU) and is increasingly used in neonatal clinical practice worldwide. Recent ultrasound-based protocols such as the Sonographic Assessment of liFe-threatening Emergencies-Revised (SAFE-R) and Crashing Neonate Protocol (CNP) offer step-by-step guidance for diagnosing and addressing reversible causes of cardiorespiratory collapse. Traditionally, pulseless electrical activity (PEA) has been diagnosed solely based on absent pulses on clinical examination, disregarding myocardial activity. However, integrating POCUS into resuscitation unveils the concept of pseudo-PEA, where cardiac motion activity is observed visually on the ultrasound but fails to generate a detectable pulse due to inadequate cardiac output. Paradoxically, existing neonatal resuscitation protocols lack directives for identifying and effectively leveraging pseudo-PEA insights in infants, limiting their potential to enhance outcomes. Pseudo-PEA is extensively described in adult literature owing to routine POCUS use in resuscitation. This review article comprehensively evaluates the adult pseudo-PEA literature to glean insights adaptable to neonatal care. Additionally, we propose a simple strategy to integrate POCUS during neonatal resuscitation, especially in infants who do not respond to routine measures. CONCLUSION: Pseudo-PDA is a newly recognized diagnosis in infants with the use of POCUS during resuscitation. This article highlights the importance of cross-disciplinary learning in tackling emerging challenges within neonatal medicine. WHAT IS KNOWN: • Point-of-Care ultrasound (POCUS) benefits adult cardiac arrest management, particularly in distinguishing true Pulseless Electrical Activity (PEA) from pseudo-PEA. • Pseudo-PEA is when myocardial motion can be seen on ultrasound but fails to generate palpable pulses or sustain circulation despite evident cardiac electrical activity. WHAT IS NEW: • Discuss recognition and management of pseudo-PEA in infants. • A proposed algorithm to integrate POCUS into active neonatal cardiopulmonary resuscitation (CPR) procedures.

Accuracy of Wireless Pulse Oximeter on Preterm or <2.5 kg Infants.

OBJECTIVE: Monitoring heart rate (HR) and oxygen saturation (SpO2) in infants is essential in the neonatal intensive care unit. Wireless pulse oximeter technology has been advancing but with limited accuracy data on preterm infants. This observational study compared HR and SpO2 of the wireless Owlet Smart Sock 3 (OSS3) to the wired Masimo SET (Masimo) pulse oximeter in preterm or <2.5 kg infants. STUDY DESIGN: Twenty-eight eligible infants were enrolled. They weighed between 1.7 and 2.5 kg and were without anomalies or medical instability. OSS3 and Masimo simultaneously monitored HR and SpO2 for 60 minutes. The data were aligned by time epoch and filtered for poor tracings. The agreement was compared using the Pearson's correlation coefficient, the Bland-Altman method, average root mean square (ARMS), and prevalence and bias adjusted kappa (PABAK) analyses. RESULTS: Two infants' data were excluded due to motion artifacts or device failures. The corrected gestational age and current weights were 35 ± 3 weeks and 2.0 ± 0.2 kg (mean ± standard deviation), respectively. Over 21 hours of data showed that HR was strongly correlated between the two devices (r = 0.98, p < 0.001), with a difference of -1.3 beats per minute (bpm) and the limit of agreement (LOA) -6.3 to 3.4 bpm based on the Bland-Altman method. SpO2 was positively correlated between the two devices (r = 0.71, p < 0.001) with a SpO2 bias of 0.3% (LOA: -4.6 to 4.5%). The estimated ARMS of OSS3 compared with Masimo was 2.3% for SpO2 in the 70 to 100% range. The precision decreased with lower SpO2. A strong agreement (PABAK = 0.94) was between the two devices on whether SpO2 was above or below 90%. CONCLUSION: OSS3 provided comparable HR and SpO2 accuracy to Masimo in preterm or <2.5 kg infants. Motion artifacts, lack of arterial blood gas comparisons, and lack of racial and ethnic diversity are the study limitations. More OSS3 data on the Lower HR and SpO2 ranges were needed before implementing inpatient use. KEY POINTS: · Pulse oximeters are vital for monitoring preterm infants' HR and SpO2 levels.. · Limited data exist on the accuracy of the wireless OSS3 on preterm infants.. · This observational study found that the OSS3 is comparable to the Masimo SET in measuring HR and SpO2 in preterm or <2.5 kg infants..

Thermoregulation-Focused Implementation of Delayed Cord Clamping among <34 Weeks' Gestational Age Neonates.

OBJECTIVE: Delayed cord clamping (DCC) is recommended for all neonates; however, adapting such practice can be slow or unsustainable, especially among preterm neonates. During DCC neonates are exposed to a cool environment, raising concerns for neonatal hypothermia. Moderate hypothermia may induce morbidities that counteract the potential benefits of DCC. A quality improvement project on a thermoregulation-focused DCC protocol was implemented for neonates less than 34 weeks' gestational age (GA). The aim was to increase the compliance rate of DCC while maintaining normothermia. STUDY DESIGN: The DCC protocol was implemented on October 1, 2020 in a large Level III neonatal intensive care unit. The thermoregulation measures included increasing delivery room temperature and using heat conservation supplies (sterile polyethylene suit, warm towels, and thermal pads). Baseline characteristics, the compliance rate of DCC, and admission temperatures were compared 4 months' preimplementation and 26 months' postimplementation RESULTS: The rate of DCC increased from 20% (11/54) in preimplementation to 57% (240/425) in postimplementation (p < 0.001). The balancing measure of admission normothermia remained unchanged. In a postimplementation subgroup analysis, the DCC cohort had less tendency to experience admission moderate hypothermia (<36°C; 9.2 vs. 14.1%, p = 0.11). The DCC cohort had more favorable secondary outcomes including higher admission hematocrit, less blood transfusions, less intraventricular hemorrhage, and lower mortality. Improving the process measure of accurate documentation could help to identify implementation barriers. CONCLUSION: Performing DCC in preterm neonates was feasible and beneficial without increasing admission hypothermia. KEY POINTS: · Thermoregulation-focused DCC protocol was implemented to increase DCC while maintaining normothermia.. · DCC rate increased from 20 to 57% while admission normothermia rate remained the same.. · DCC practice on preterm neonates is safe and feasible while maintaining normothermia..

"All I Can Say Is Thank You": A Qualitative Study of Gratitude in the NICU Before and During COVID-19.

BACKGROUND: COVID-19-associated visitor restrictions altered parents' involvement in their infant's care in the neonatal intensive care unit (NICU). PURPOSE: The purpose of this article is to explore how restrictions affected parents' perceptions of experience in the NICU and to build a conceptual model of communication flow during times of crisis. METHODS: This qualitative study was set in a level III 52-bed NICU. Using data from an open-ended survey question, a multitiered thematic analysis was used. RESULTS: Four broad themes emerged: communication, gratitude, release, and containment of emotionality. These 4 themes interacted codependently and manifested differently as COVID-related visitor policies were put in place. Parents' characterization of communication also varied depending on the visitation policies. Before COVID, parents were more likely to reflect on communication. During COVID, parents expressed more gratitude, while containing negative emotions-sometimes using gratitude to soften the blow of bad feedback. IMPLICATIONS FOR PRACTICE AND RESEARCH: Our theoretical model suggests that gratitude may serve as a form of "reciprocal care" to providers during a period of crisis and extreme stress. Use of high-quality communication between providers and parents in the NICU is necessary to understand parental concerns or negative experience.

Diagnosis and management of phyllodes tumours for the surgeon: An algorithm.

A Phyllodes Tumour (PT) is an uncommon fibroepithelial lesion, with three histological grades - benign, borderline and malignant. PTs cause significant challenges in diagnosis, management and prognostication. Recent publications have clarified the definitions and prognostication of PTs. Contemporary data currently challenge international guidelines on PT management. We performed an in-depth literature review to develop a best-practice management algorithm for PTs. Diagnostic recommendations are that neither current imaging techniques, nor fine-needle biopsies, can reliably diagnose a PT. Core needle biopsy is the optimal diagnostic technique. Indeterminate or suspicious lesions are recommended to undergo an excisional biopsy due to the inherently heterogeneous nature of PTs. Management guidelines are that benign PTs should be completely excised, although an involved margin is acceptable in select situations. Borderline PTs should have a clear margin on excision due to their higher risk of recurrence, as well as the potential for a recurrence to progress to a malignant PT. In malignant PTs, a margin of 3 mm is acceptable as there is no reduction in recurrence risk if margins are >3 mm. Routine axillary surgery is not indicated in PTs, with axillary surgery only indicated in a histologically-confirmed positive axilla. Adjuvant treatment recommendations are that borderline and malignant PTs should be discussed at MDT, with radiotherapy considered in both. Chemotherapy should be discussed in malignant PT patients. In summary, we have developed an up-to-date simple algorithm to guide the surgeon's management of patients diagnosed with PTs and reduce excessive surgery.

Customized Three-Dimensional Printed Splints for Neonates in the Neonatal Intensive Care Unit: Three Case Reports.

IMPORTANCE: Critically ill neonates can be vulnerable to positional deformities and joint contractures. Early splints, along with dynamic exercise, may lead to long-term functional improvement. Making splints to perfectly contour neonates' small joints and bodies is challenging. An ill-fitted splint can lead to skin ulcers, nerve damage, poor compliance, and discomfort. Three-dimensional (3D) printing has been applied to create customized, cost-effective, and lightweight orthoses that may be promising for neonates. OBJECTIVE: To explore the feasibility of scanning, designing, and printing 3D splints for neonates. SETTING: A large neonatal intensive care unit (NICU) in a university teaching hospital. METHOD: Case series of three neonates in a NICU who had deformities or joint contractures that would benefit from early static splints. We created customized splints for neonates using 3D scanning, digital design software, and 3D printing technology. We monitored the neonates' comfort and clinical improvement. RESULTS: One neonate with a congenital neck deformity had a neck splint created from 3D body-scanned images. Another neonate with a hand deformity was measured and had 3D digitally designed hand splints made. The same hand splint design was modified to fit a third neonate's hand with new measurements. All splints were 3D printed using specialized lightweight materials. The neonates tolerated the splints well. CONCLUSIONS AND RELEVANCE: 3D printing technology is feasible for and applicable to NICU neonates. Advancing 3D technology should focus on upgrading scanning quality, improving splint design, and speeding up printing. Further research to evaluate the long-term benefits of early splinting is needed. What This Article Adds: This is the first published article to discuss the feasibility of using 3D printing technology to create customized splints for fragile neonates. Neonates, especially critically ill ones with congenital defects, may benefit from early splinting to preserve function and development. Neonates are the most challenging patients to make a perfect-fit splint for, and 3D printing may offer a potential solution.

Association of Intrapartum Drugs with Spontaneous Intestinal Perforation: A Single-Center Retrospective Review.

OBJECTIVE: Spontaneous intestinal perforation (SIP) occurs commonly in extremely low gestational age newborns (ELGANs; <30 weeks' GA). Early, concurrent neonatal use of indomethacin (Neo_IN) and hydrocortisone (Neo_HC) is a known risk for SIP. Mothers in premature labor often receive indomethacin (Mat_IN) for tocolysis and steroids (Mat_S) for fetal maturation. Coincidentally, ELGANs may receive Neo_IN or Neo_HC within the first week of life. There are limited data on the effect of combined exposures to maternal and neonatal medications. We hypothesized that proximity exposure to these medications may increase the risk of SIP. STUDY DESIGN: We reviewed the medical records of ELGANs from June 2014 to December 2019 at a single level III neonatal intensive care unit. We compared antenatal and postnatal indomethacin and steroid use between neonates with and without SIP. For analysis, chi-square, Student's t-test, Fisher's exact test, and Mann-Whitney U tests were used. RESULTS: Among 417 ELGANs, SIP was diagnosed in 23, predominantly in neonates < 26 weeks' GA (n = 21/126, 16.7%). Risk factors analysis focused on this GA cohort in which SIP was most prevalent. Mat_IN administration within 2 days of delivery increased SIP risk (odds ratio: 3; 95% confidence interval: 1.25-7.94; p = 0.036). Neo_HC was not independently associated with SIP (p = 0.38). A higher proportion of SIP group had close temporal exposure of Mat_IN and Neo_HC compared with the non-SIP group, though not statistically significant (14 vs. 7%, p = 0.24). CONCLUSION: Peripartum Mat_IN was associated with increased risk for SIP in this small study sample. Larger studies are needed to further delineate SIP risk from the interaction of peripartum maternal medication with early postnatal therapies and disease pathophysiology. KEY POINTS: · Perinatal indomethacin is associated with SIP in preterm infants born at less than 26 weeks.. · Temporal proximity of prenatal/postnatal medication exposure matters.. · Indomethacin and Hydrocortisone the risks, benefits, and timing related to SIP..

An Evaluation to Establish the Acceptable Serum Triglyceride Levels in Neonates Receiving Intravenous Fat Emulsion Infusion in a Multicenter Retrospective Study.

OBJECTIVE: This study aimed to establish neonatal serum triglyceride (TG) level reference ranges during lipid infusion and correlate peak TG with neonatal outcomes. STUDY DESIGN: This is a retrospective review of 356 neonates with 696 TG measures obtained in four neonatal intensive care units between 2015 and 2017. TG was evaluated collectively to establish a reference range and a threshold limit. To analyze the effects of a higher TG threshold, neonates were categorized by their peak TG: <180 (TG<180), 180 to 400 (TG180-400), and > 400 mg/dL (TG>400). Univariable and multivariable regression models were constructed to compare peak TG to patient characteristic and clinical outcomes. RESULTS: The frequency of TG > 400 mg/dL was 5% and found only in neonates weighing < 1.5 kg. Neonates in the TG180-400 (n = 91) group were significantly lower in birth weight and gestational age, had lower 5-minute APGAR scores, and had increased ventilatory requirement when compared with neonates in the TG<180 (n = 240) group (all p < 0.001). The TG180-400 group had increased risk of severe intraventricular hemorrhage (p = 0.02) and bronchopulmonary dysplasia (p = 0.03). Elevated TG was associated with mortality (odds ratio [OR]: 14.4, p < 0.001) in univariable analysis, but the relationship weakened (OR: 4.4, p = 0.05) after adjusting for comorbidities in multivariable logistic regression. CONCLUSION: It is unclear if the adverse outcomes seen in neonates with higher peak TG were due to elevated TG alone, or whether illness severity predicted the increased TG. More prospective studies are needed to further delineate the relationships.

Abdominal Ultrasound Assists the Diagnosis and Management of Necrotizing Enterocolitis.

BACKGROUND: Abdominal x-ray (KUB) routinely aids in detecting necrotizing enterocolitis (NEC), one of the most serious neonatal intestinal diseases. However, a KUB may miss up to 50% of the early signs of NEC. Recent advances in abdominal ultrasound (AUS) can expedite this diagnosis and improve clinical management. PURPOSES: To illustrate AUS findings that suggest NEC through 3 case examples. To review current literature regarding advantages and limitations of AUS compared with KUB. RESULTS: The added visualization of intra-abdominal structures with AUS compared with KUB improves the diagnosis and management of NEC. Some AUS features are highly suggestive of impending bowel perforation, while others can confirm bowel perforation despite a negative radiograph. IMPLICATIONS FOR PRACTICE: AUS expedites time to diagnosis of NEC and helps to stratify patients who may fail medical management and require surgical intervention. IMPLICATIONS FOR RESEARCH: More quality improvement studies are needed to validate an AUS protocol for the management of NEC. Advances in technology, such as contrast-enhanced ultrasound, may improve NEC detection with AUS in the future.Video Abstract available athttps://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

A Quality Improvement Approach to Perineal Skin Care: Using Standardized Guidelines and Novel Diaper Wipes to Reduce Diaper Dermatitis in NICU Infants.

BACKGROUND: Diaper dermatitis (DD) causes discomfort and emotional distress and creates possible sources of infection among newborn intensive care unit infants. Diaper dermatitis remains prevalent despite studies documenting an understanding of prevention and treatment modalities. Standardizing perineal skin care guidelines could reduce DD. PURPOSE: Implement perineal skin care guidelines, while introducing novel diaper wipes, to decrease the incidence of DD by 20% within a 1-year period. METHODS: Our unit reviewed evidence-based literature to develop a standardized perineal care guideline for prevention and treatment, encompassing the use of novel, preservative-free diaper wipes with grapefruit seed extract. The outcome measures were the incidence and duration of DD. Process compliances were monitored. The balancing measure was the rate of fungal skin infection while using preservative-free wipes. FINDINGS: Between July 2017 and March 2019, 1070 infants were admitted for 1 or more days, with 11% of those being born at less than 30 weeks of gestational age. After guideline implementation in January 2018, the incidence of DD decreased by 16.7%. The incidence of severe cases dropped by 34.9%, with 3.5 days per 100 patient-days shortened duration. Process compliance was achieved. Neonates tolerated the novel wipes without increased fungal skin infection. IMPLICATIONS FOR PRACTICE: The Perineal Skin Care Guidelines could reduce the rate and duration of DD. Newborn intensive care unit infants tolerated the novel diaper wipes. IMPLICATIONS FOR RESEARCH: Additional research on wipes containing other types of extracts or ingredients.

The Beneficence of Cuddle Therapy in Hyperekplexia: A Case Report.

BACKGROUND: Benevolent injustice occurs when well-intentioned treatment efforts produce an outcome that limits the potential of a patient. The unintended harm can result in significant moral distress for the family and the healthcare team. CLINICAL FINDINGS: We discussed an ethical dilemma regarding a neonate who had suspected seizure and hypoxic-ischemic encephalopathy after home birth delivery. The healthcare team experienced moral distress about the mother's desire to not use anti-seizure medications and instead trial other interventions such as cuddling. Subsequently, clinical analysis ruled out a seizure disorder. Genetic studies on this neonate confirmed hereditary hyperekplexia, which presented as exaggerated Moro reflex and apnea that mimicked seizure. INTERVENTION: We discussed how applying any one of the 4 basic ethical principles of autonomy, beneficence, nonmaleficence, or justice could counteract benevolent injustice and moral distress. OUTCOMES: Discussions with the patient's mother and nurse allowed the team to overcome their reluctance to try the mother's treatment recommendations. This resulted in adopting the seemingly counterintuitive intervention of cuddling that turned out to be effective for this neonate with hereditary hyperekplexia. PRACTICE RECOMMENDATIONS: The moral distress associated with benevolent injustice should be identified early to minimize long-term consequences to the patient, family, and healthcare team. Healthcare teams should learn to apply ethical principles when discussing patient care concerns in an unbiased manner. Guided ethical discussions allow us to be more efficient in providing family-centered care that aligns with the patient's best interest.

The Extended Dwell Peripheral Intravenous Catheter Is an Alternative Method of NICU Intravenous Access.

BACKGROUND: Establishing vascular access is a common neonatal intensive care unit procedure. The extended dwell peripheral intravenous (EPIV) catheter is a 6-cm and 8-cm silicone catheter for peripheral vein insertion, which is a newer vascular access device than peripherally inserted central catheters (PICCs) and peripheral intravenous (PIV) catheter. Extended dwell peripheral intravenous catheters have been widely used in adults but evidence in neonates is lacking. PURPOSE: To explore indwell time, success rate, catheter-associated complications, and cost among EPIV catheters, PICCs, and PIV catheters in neonates. METHODS: We retrospectively compare patient demographics, indwell time, success rate, and catheter-associated complications, and analyze the rate of hyaluronidase-treated intravenous (IV) fluid extravasation on neonates who had an EPIV catheter, a PICC, or a PIV catheter in a level III neonatal intensive care unit. We also estimate the insertion cost of these 3 vascular access devices on the basis of our hospital charges. RESULTS: Extended dwell peripheral intravenous catheters were inserted in 432 neonates with an indwell time of 4.0 ± 2.3 (mean ± SD) days. Peripherally inserted central catheters were inserted in 202 neonates with an average indwell time of 7.3 ± 4.4 (mean ± SD) days, which was longer than EPIV catheters (P < .001). Peripherally inserted central catheters had a higher success rate of 83.6% than 71.7% of EPIV catheters, meaning succeeded in lasting through the completion of therapy (P = .001). Peripherally inserted central catheters were associated with 4 cases of life-threatening complications; none was seen in the EPIV catheter group. The incidence of hyaluronidase-treated IV fluid extravasation was less in EPIV catheter recipients (1.2%) than in the PIV catheter recipients (3.9%) (P = .004); none was in the PICC group. Cost savings were noted with using an EPIV catheter. IMPLICATIONS FOR PRACTICE: Extended dwell peripheral intravenous catheter is a feasible option for neonatal vascular access. IMPLICATIONS FOR RESEARCH: These data provide a baseline for future studies to explore the efficacy and effectiveness of EPIV catheter in the neonates.

Apc deficiency alters pulmonary epithelial cell fate and inhibits Nkx2.1 via triggering TGF-beta signaling.

Wnt signaling is critical for cell fate specification and cell differentiation in many organs, but its function in pulmonary neuroendocrine cell (PNEC) differentiation has not been fully addressed. In this study, we examined the role of canonical Wnt signaling by targeting the gene for Adenomatous Polyposis Coli (Apc), which controls Wnt signaling activity via mediating phosphorylation of beta-catenin (Ctnnb). Targeting the Apc gene in lung epithelial progenitors by Nkx2.1-cre stabilized Ctnnb and activated canonical Wnt signaling. Apc deficiency altered lung epithelial cell fate by inhibiting Clara and ciliated cell differentiation and activating Uchl1, a marker of neuroendocrine cells. Similar to PNEC in normal lung, Uchl1(positive) cells were innervated. In mice with targeted inactivation of Ctnnb by Nkx2.1-cre, PNEC differentiation was not interrupted. These indicate that, after lung primordium formation, Wnt signaling is not essential for PNEC differentiation; however, its over-activation promotes PNEC features. Interestingly, Nkx2.1 was extinguished in Apc deficient epithelial progenitors before activation of Uchl1. Examination of Nkx2.1 null lungs suggested that early deletion of Nkx2.1 inhibits PNEC differentiation, while late repression does not. Nkx2.1 was specifically inhibited in Apc deficient lungs but not in Ctnnb gain-of-function lungs indicating a functional difference between Apc deletion and Ctnnb stabilization, both of which activate Wnt signaling. Further analysis revealed that Apc deficiency led to increased TGF-beta signaling, which inhibited Nkx2.1 in cultured lung endodermal explants. In contrast, TGF-beta activity was not increased in Ctnnb gain-of-function lungs. Therefore, our studies revealed an important mechanism involving Apc and TGF-beta signaling in regulating the key transcriptional factor, Nkx2.1, for lung epithelial progenitor cell fate determination.

Breast conservation versus mastectomy for metaplastic breast cancer: A systematic review and meta-analysis.

Metaplastic breast cancer is a rare aggressive subtype of breast cancer for which there are no clear treatment guidelines regarding the optimal surgical approach. This systematic review and meta-analysis aimed to evaluate survival outcomes of patients with metaplastic breast cancer undergoing breast conservation compared with mastectomy. We identified studies from MEDLINE, Pubmed, EMBASE, Google Scholar, the Cochrane Library Register of Controlled Trials and the EBM Reviews Register. Studies were deemed suitable for inclusion where they compared breast-conserving surgery to mastectomy with the primary outcome of overall survival. Survival data were pooled using a random-effects model. From the 456 citations screened by our search, three studies were assessed as eligible for inclusion. There were a total of 2995 patients who underwent mastectomy and 1909 who underwent breast conservation. The median follow-up time was 43 months. Meta-analysis demonstrated no significant difference between breast conservation and mastectomy (pooled HR 0.89, 95% CI, 0.56-1.42, p = 0.631). Wide local excision, in conjunction with adjuvant radiation and judicious use of chemotherapy, may be a reasonable alternative to mastectomy as surgical management of metaplastic breast cancer as part of an individualized, multidisciplinary approach.

Radar localization of breast and axillary lesions with SCOUT: a prospective single institution pilot study.

BACKGROUND: Wire-guided localization has been the mainstay of localization techniques for non-palpable breast and axillary lesions prior to excision. Evidence is still growing for relatively newer localization technologies. This study evaluated the efficacy of the wireless localization technology, SCOUT®, for both breast and axillary surgery. METHODS: Data were extracted from a prospective database (2021-2023) of consecutive patients undergoing wide local excision, excisional biopsy, targeted axillary dissection, or axillary lymph node dissection with SCOUT at a high-volume tertiary centre. Rates of successful reflector placement, intraoperative lesion localization, and reflector retrieval were evaluated. A survey of surgeon-reported ease of lesion localization and reflector retrieval was also evaluated. CLINICAL TRIAL REGISTRATION: ACTRN386751. RESULTS: One-hundred-ninety-five reflectors were deployed in 172 patients. Median interval between deployment and surgery was 3 days (range 1-20) and mean distance from reflector to lesion was 3.2 mm (standard deviation, SD 3.1). Rate of successful localization and reflector retrieval was 100% for both breast and axillary procedures. Mean operating time was 65.8 min (SD 33). None of the reflectors migrated. No reflector deployment or localization-related complications occurred. Ninety-eight percent of surgeons were satisfied with ease of localization for the first half of cases. CONCLUSION: SCOUT is an accurate and reliable method to localize and excise both breast and axillary lesions, and it may overcome some of the limitations of wire-guided localization.