Severe Dysplasia Research Articles

Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans

ERI1 is a 3'-to-5' exoribonuclease involved in RNA metabolic pathways including 5.8S rRNA processing and turnover of histone mRNAs. Its biological and medical significance remain unclear. Here, we uncover a phenotypic dichotomy associated with bi-allelic ERI1 variants by reporting eight affected individuals from seven unrelated families. A severe spondyloepimetaphyseal dysplasia (SEMD) was identified in five affected individuals with missense variants but not in those with bi-allelic null variants, who showed mild intellectual disability and digital anomalies. The ERI1 missense variants cause a loss of the exoribonuclease activity, leading to defective trimming of the 5.8S rRNA 3' end and a decreased degradation of replication-dependent histone mRNAs. Affected-individual-derived induced pluripotent stem cells (iPSCs) showed impaired invitro chondrogenesis with downregulation of genes regulating skeletal patterning. Our study establishes an entity previously unreported in OMIM and provides a model showing a more severe effect of missense alleles thannull alleles within recessive genotypes, suggesting a key role of ERI1-mediated RNA metabolism in human skeletal patterning and chondrogenesis.

RISK ASSESSMENT OF ORAL LEUKOPLAKIA BY DNA CONTENT USING FLOW CYTOMETRY

Risk assessment for oral leukoplakia (OL) for malignant transformations (MT) has evolved as innovative strategies, considering that DNA content measurements have been providing consistent and reproducible predictive values using archived material. Such strategies are based on costly equipment and expertise, often inaccessible to underprivileged populations. This study aimed to investigate DNA content as a predictive marker of MT adapting image-based cytometry to a conventional flow cytometry (FC) context. Cases were selected from 878 biopsies, including mild, moderate, and severe dysplasia, and lesions without dysplasia. Twenty-six of these cases had undergone MT. FC was used to establish DNA content based on propidium iodide fluorescent labeling of nuclear suspensions. Spearman correlation was used for associations between dysplasia and ploidy (p <0.05). The predictive values of each marker were calculated from Kaplan-Meier and the Log-rank tests (p <0.05). Multiple logistic regression was used to enhance DNA content classification criteria for FC. Enhanced aneuploidy classification showed up to a 75% positive predictive value and a 95% negative predictive value, which are among the highest reported in the literature. In conclusion, conventional FC can be used to detect both high-risk and low-risk OL with high sensitivity and specificity. Risk assessment for oral leukoplakia (OL) for malignant transformations (MT) has evolved as innovative strategies, considering that DNA content measurements have been providing consistent and reproducible predictive values using archived material. Such strategies are based on costly equipment and expertise, often inaccessible to underprivileged populations. This study aimed to investigate DNA content as a predictive marker of MT adapting image-based cytometry to a conventional flow cytometry (FC) context. Cases were selected from 878 biopsies, including mild, moderate, and severe dysplasia, and lesions without dysplasia. Twenty-six of these cases had undergone MT. FC was used to establish DNA content based on propidium iodide fluorescent labeling of nuclear suspensions. Spearman correlation was used for associations between dysplasia and ploidy (p <0.05). The predictive values of each marker were calculated from Kaplan-Meier and the Log-rank tests (p <0.05). Multiple logistic regression was used to enhance DNA content classification criteria for FC. Enhanced aneuploidy classification showed up to a 75% positive predictive value and a 95% negative predictive value, which are among the highest reported in the literature. In conclusion, conventional FC can be used to detect both high-risk and low-risk OL with high sensitivity and specificity.

CORRELATION BETWEEN EPITHELIAL DYSPLASIA AND ORAL SQUAMOUS PAPILLOMA AS A RESULT OF MULTIPLE RISK FACTORS: A CLINICAL CASE

This study is a clinical case of a 64-year-old leukoderma female patient, smoker for more than 45 years, who, after being diagnosed with Hepatitis A and B in different periods, presented a single leukoplastic, verrucous, pedunculated nodule, of the "cauliflower" type, on the lower alveolar edge of the right side (lesion I). It also presented homogeneous leukoplastic plaque, with verrucous surface, in the region of the lateral border of the tongue on the left side (lesion II). Both lesions were asymptomatic, with an undefined onset. The probable diagnostic hypotheses were squamous papilloma (lesion I) and leukoplakia (lesion II), with a differential diagnosis of condyloma (lesion I) and lichen planus (lesion II). Biopsy was performed by excisional removal of lesion I and incisional removal of lesion II, with the diagnosis of oral squamous papilloma and moderate to severe oral epithelial dysplasia, respectively. There was no radiographic lesion. Patient is undergoing follow-up. This study is a clinical case of a 64-year-old leukoderma female patient, smoker for more than 45 years, who, after being diagnosed with Hepatitis A and B in different periods, presented a single leukoplastic, verrucous, pedunculated nodule, of the "cauliflower" type, on the lower alveolar edge of the right side (lesion I). It also presented homogeneous leukoplastic plaque, with verrucous surface, in the region of the lateral border of the tongue on the left side (lesion II). Both lesions were asymptomatic, with an undefined onset. The probable diagnostic hypotheses were squamous papilloma (lesion I) and leukoplakia (lesion II), with a differential diagnosis of condyloma (lesion I) and lichen planus (lesion II). Biopsy was performed by excisional removal of lesion I and incisional removal of lesion II, with the diagnosis of oral squamous papilloma and moderate to severe oral epithelial dysplasia, respectively. There was no radiographic lesion. Patient is undergoing follow-up.

Pain, function and quality of life are impaired in adults undergoing periacetabular osteotomy (PAO) for hip dysplasia: a systematic review and meta-analysis.

Hip dysplasia is a common condition in active adults with hip pain that can lead to joint degeneration. Periacetabular osteotomy (PAO) is a common surgical treatment for hip dysplasia. The effect of this surgery on pain, function and quality of life (QOL) has not been systematically analysed. In adults with hip dysplasia: (1) evaluate differences in pain, function and QOL in those undergoing PAO and healthy controls; (2) evaluate pre- to post-PAO changes in pain, function and QOL; (3) evaluate differences in pain, function and QOL in those with mild versus severe dysplasia, undergoing PAO; and (4) evaluate differences in pain, function and QOL in those having primary PAO versus those with previous hip arthroscopy. A comprehensive, reproducible search strategy was performed on 5 different databases. We included studies that assessed pain, function and QOL in adults undergoing PAO for hip dysplasia, using hip-specific patient reported outcomes measures. From 5017 titles and abstracts screened, 62 studies were included. Meta-analysis showed PAO patients had worse outcomes pre- and post-PAO compared to healthy participants. Specifically, pain (standardised mean difference [SMD] 95% confidence interval [CI]): -4.05; -4.78 to -3.32), function (-2.81; -3.89 to -1.74), and QOL (-4.10; -4.43 to -3.77) were significantly poorer preoperatively.Meta-analysis found patients experienced improvements following PAO. Pain improved from pre-surgery to 1-year (standardised paired difference [SPD] 1.35; 95% CI, 1.02-1.67) and 2 years postoperatively (1.35; 1.16-1.54). For function, the activities of daily living scores at 1 year (1.22; 1.09-1.35) and 2 years (1.06; 0.9-1.22) and QOL at 1 year (1.36; 1.22-1.5) and 2 years (1.3; 1.1-1.5) all improved. No difference was found between patients undergoing PAO with mild versus severe dysplasia. Before undergoing PAO surgery, adults with hip dysplasia have worse levels of pain, function and QOL compared to healthy participants. These levels improve following PAO, but do not reach the same level as their healthy participants. PROSPERO (CRD42020144748).

One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004–2007, 2014–2016 and 2017–2019

ObjectiveTo explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden.Design/SettingData on all births at 22 and 23 weeks’ gestational age...

Bone Growth Induction in Mucopolysaccharidosis IVA Mouse.

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is caused by a deficiency of the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) enzyme, leading to the accumulation of glycosaminoglycans (GAG), keratan sulfate (KS) and chondroitin-6-sulfate (C6S), mainly in cartilage and bone. This lysosomal storage disorder (LSD) is characterized by severe systemic skeletal dysplasia. To this date, none of the treatment options for the MPS IVA patients correct bone pathology. Enzyme replacement therapy with elosulfase alpha provides a limited impact on bone growth and skeletal lesions in MPS IVA patients. To improve bone pathology, we propose a novel gene therapy with a small peptide as a growth-promoting agent for MPS IVA. A small molecule in this peptide family has been found to exert biological actions over the cardiovascular system. This work shows that an AAV vector expressing a C-type natriuretic (CNP) peptide induces bone growth in the MPS IVA mouse model. Histopathological analysis showed the induction of chondrocyte proliferation. CNP peptide also changed the pattern of GAG levels in bone and liver. These results suggest the potential for CNP peptide to be used as a treatment in MPS IVA patients.

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. Translation research. Affiliated Hospital of University. Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

Association of Trochlear Length on Sagittal MRI to Trochlear Dysplasia in Knees With Patellar Instability.

Trochlear dysplasia is a primary risk factor for patellar instability and leads to loss of the osteochondral constraint of the patella. Trochleoplasty techniques include the Peterson grooveplasty, which alters the length of the trochlea; however, a radiographic measurement of trochlear length to support this has not been described. To describe measurements to quantify trochlear length on sagittal magnetic resonance imaging in patients with and without patellar instability and to correlate trochlear length with measurements of trochlear dysplasia. Cross-sectional study; Level of evidence, 3. A total of 66 age- and sex-matched knees (36 female and 30 male; mean age, 20.8 ± 4.8 years) were included in this study, of which 33 had patellar instability. Trochlear extension length (TEL) and trochlear alpha angle (TAA) were measured on 3 sagittal magnetic resonance imaging scans (center of the knee, center of the medial condyle, and center of the lateral condyle), and measurements were compared between symptomatic and control knees. Receiver operating characteristic curve analysis was performed, and the area under the curve (AUC) was calculated to describe the accuracy of each measurement to distinguish between knees with and without patellar instability. Linear and multivariate regression analyses were performed to assess the relationship between sagittal measurements and axial measurements of trochlear dysplasia, including lateral trochlear inclination, sulcus angle, and trochlear depth, as well as patient size reflected by the epicondylar distance. In symptomatic knees, the central trochlea extended more proximally than in control knees, as determined by the TEL (14.0 ± 3.0 vs 11.5 ± 2.3 mm, respectively; P < .001) and TAA (68.4° ± 3.8° vs 70.5° ± 3.4°, respectively; P = .017). AUC calculations showed that a TEL ≥11 mm at the central trochlea was predictive of patellar instability in both male and female knees (AUC = 0.83 and 0.77, respectively), as was a TAA ≤67° in female knees (AUC = 0.72). An independent association between the central TEL and sulcus angle was found. The central TEL showed a weak correlation with patient size, as measured by the epicondylar distance, while the TAA did not. In knees with symptomatic patellar instability, the central trochlea was found to extend 2.5 mm more proximally than in control knees, and this increase in length correlated with severity of trochlear dysplasia. As radiographic examinations of the trochlea and grooveplasty procedures are often based on the proximal extent of the cartilaginous trochlea, further studies are needed to identify the role of trochlear length in the assessment and treatment of trochlear dysplasia in the setting of patellar instability.

Profiles and Findings of Population-Based Esophageal Cancer Screening With Endoscopy in China: Systematic Review and Meta-analysis.

Population-based esophageal cancer (EC) screening trials and programs have been conducted in China for decades; however, screening strategies have been adopted in different regions and screening profiles are unclear. We performed a meta-analysis to profile EC screening in China by positivity rate, compliance rate, and endoscopy findings, aiming to provide explicit evidence and recommendations for EC screening programs. English (PubMed, Embase) and Chinese (China National Knowledge Infrastructure, Wanfang) language databases were systematically searched for population-based EC screening studies in the Chinese population until December 31, 2022. A meta-analysis was performed by standard methodology using a random-effects model. Pooled prevalence rates were calculated for three groups: high-risk areas with a universal endoscopy strategy, rural China with a risk-stratified endoscopic screening (RSES) strategy, and urban China with an RSES strategy. Positive cases included lesions of severe dysplasia, carcinoma in situ, intramucosal carcinoma, submucosal carcinoma, and invasive carcinoma. The pooled positivity rate of the high-risk population was higher in rural China (44.12%) than in urban China (23.11%). The compliance rate of endoscopic examinations was the highest in rural China (52.40%), followed by high-risk areas (50.11%), and was the lowest in urban China (23.67%). The pooled detection rate of positive cases decreased from 1.03% (95% CI 0.82%-1.30%) in high-risk areas to 0.48% (95% CI 0.25%-0.93%) in rural China and 0.12% (95% CI 0.07%-0.21%) in urban China. The pooled detection rate of low-grade intraepithelial neoplasia (LGIN) was also in the same order, being the highest in high-risk areas (3.99%, 95% CI 2.78%-5.69%), followed by rural China (2.55%, 95% CI 1.03%-6.19%) and urban China (0.34%, 95% CI 0.14%-0.81%). Higher detection rates of positive cases and LGIN were observed among males than among females and at older ages. The pooled early detection rate was 81.90% (95% CI 75.58%-86.88%), which was similar to the rates in high-risk areas (82.09%), in rural China (80.76%), and in urban China (80.08%). Under the current screening framework, a higher screening benefit was observed in high-risk areas than in other regions. To promote EC screening and reduce the current inequality of screening in China, more focus should be given to optimizing strategies of high-risk individual assessment and surveillance management to improve compliance with endoscopic examination. PROSPERO CRD42022375720; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375720.

NOVAprep-miR-Cervix: New Method for Evaluation of Cervical Dysplasia Severity Based on Analysis of Six miRNAs.

Cervical cancer is one of the most common gynecological malignancies and it is preventable through the yearly diagnosis and management of pre-cancerous cervical disease. The profile of miRNA expression in cervical epithelium cells is altered with cervical dysplasia development and further progression. The NOVAprep-miR-CERVIX is a new approach for the assessment of cervical dysplasia through the analysis of six marker miRNAs. This study aims to evaluate theperformance and diagnostic potency of the new method. Cytological smears from 226 women (NILM, n.114; HSIL, n.112) were included in the study. A VPH test was performed with RealBest DNAHPV HR screen Kit, six marker miRNAs (miR-21, -29b, -145, -451a, -1246, -1290) were assayed using NOVAprep-miR-CERVIX kit. Obtained data were analyzed using the Delta Ct method and random forest machine learning algorithm. The results of the quantitative analysis of six microRNAs were expressed as a miR-CERVIX parameter, which ranged from 0 to 1, where "0" corresponded to the healthy cervical epithelium, while "1" corresponded to high-grade squamous intraepithelial dysplasia. The average value of miR-CERVIX differed in groups of NILM and HSIL samples (0.34 vs. 0.72; p < 0.000005). An estimation of miR-CERVIX allowed for the differentiation between healthy and pre-cancerous samples with sensitivity of 0.79 and specificity of 0.79, as well as to confirm HSIL with specificity of 0.98. Interestingly, the HSIL group included HPV(+) and HPV(-) samples, which were statistically significantly different in terms of miR-CERVIX value. Analysis of CC-associated miRNAs in material of cervical smear might serve as an additional method for the evaluation of cervical dysplasia severity.

Impact of Early Hemodynamic Screening on Extremely Preterm Outcomes in a High-Performance Center.

Rationale: Increasing survival of extremely preterm infants with a stable rate of severe intraventricular hemorrhage represents a growing health risk for neonates. Objectives: To evaluate the role of early hemodynamic screening (HS) on the risk of death or severe intraventricular hemorrhage. Methods: All eligible patients 22-26+6 weeks' gestation born and/or admitted <24 hours postnatal age were included. As compared with standard neonatal care for control subjects (January 2010-December 2017), patients admitted in the second epoch (October 2018-April 2022) were exposed to HS using targeted neonatal echocardiography at 12-18 hours. Measurements and Main Results: A primary composite outcome of death or severe intraventricular hemorrhage was decided a priori using a 10% reduction in baseline rate to calculate sample size. A total of 423 control subjects and 191 screening patients were recruited with a mean gestation and birth weight of 24.7 ± 1.5 weeks and 699 ± 191 g, respectively. Infants born at 22-23 weeks represented 41% (n = 78) of the HS epoch versus 32% (n = 137) of the control subjects (P = 0.004). An increase in perinatal optimization (e.g., antepartum steroids) but with a decline in maternal health (e.g., increased obesity) was seen in the HS versus control epoch. A reduction in the primary outcome and each of severe intraventricular hemorrhage, death, death in the first postnatal week, necrotizing enterocolitis, and severe bronchopulmonary dysplasia was seen in the screening era. After adjustment for perinatal confounders and time, screening was independently associated with survival free of severe intraventricular hemorrhage (OR 2.09, 95% CI [1.19, 3.66]). Conclusions: Early HS and physiology-guided care may be an avenue to further improve neonatal outcomes; further evaluation is warranted.

Neonatal Intensive Care Unit Patients Receiving More Than 25 Platelet Transfusions.

A few patients in neonatal intensive care units (NICU) receive numerous platelet transfusions. These patients can become refractory, defined as transfusions of ≥10 mL/kg failing to increase the platelet count by at least 5,000/µL. Causes of, and best treatments for, platelet transfusion refractoriness in neonates have not been defined. Multi-NICU multiyear retrospective analysis of neonates receiving >25 platelet transfusions. Eight neonates received 29 to 52 platelet transfusions. All eight were blood group O. Five had sepsis, four were very small for gestational age, four had bowel resections, two Noonan syndrome, two had cytomegalovirus infection. All eight had some (19-73%) refractory transfusions. Many (2-69%) of the transfusions were ordered when the platelet count was >50,000/µL. Higher posttransfusion counts occurred after ABO-identical transfusions (p = 0.026). Three of the eight had late NICU deaths related to respiratory failure; all five survivors had severe bronchopulmonary dysplasia requiring tracheostomy for prolonged ventilator management. Neonates who are high users of platelet transfusions appear to be at high risk for poor outcomes, especially respiratory failure. Future studies will examine whether group O neonates are more likely to develop refractoriness and whether certain neonates would have a higher magnitude of posttransfusion rise if they received ABO-identical donor platelets. · Many of the platelet transfusions given in the NICU are given to a small subset of patients.. · Refractoriness to platelet transfusions is common among these very high recipients.. · Neonates who are high users of platelet transfusions appear to be at high risk for poor outcomes..

VEGFA rs3025039 is associated with phenotype severity of myelofibrosis-type megakaryocyte dysplasia.

VEGFA rs3025039 is associated with phenotype severity of myelofibrosis-type megakaryocyte dysplasia.

Lung biopsy in infants with severe bronchopulmonary dysplasia.

Lung biopsy is infrequently performed in the population of infants with severe bronchopulmonary dysplasia (BPD). Yet, its presentation may overlap with other infant diffuse lung diseases, including those within the spectrum of childhood interstitial lung diseases (chILD). Lung biopsy might differentiate between these entities or identify those with an extremely poor prognosis. Both might alter the clinical management of some infants diagnosed with BPD. In this tertiary referral center, we drew on a retrospective cohort of 308 preterm infants with severe BPD. Of these, nine underwent lung biopsy between 2012 and 2017. We aimed to assess the indication for lung biopsy, the prior clinical history, safety of the procedure, and describe the biopsy findings. Finally, we considered management decisions in relation to the biopsy results in these patients. All nine infants undergoing biopsy survived the procedure. The mean gestational age and birth weight of the nine patients were 30 ± 3 (range 27-34) weeks and 1421 ± 571 (range 611-2140) grams. All infants received serial echocardiograms to assess pulmonary hypertension, genetic testing, and computed tomography angiography (CTA) before biopsy. In all nine patients moderate to severe alveolar simplification was present and eight had some degree of pulmonary interstitial glycogenosis (PIG) ranging from focal to diffuse. Following biopsy, two infants with PIG received high dose systemic steroids and two separate infants had care redirected. In our cohort, lung biopsy was safe and well tolerated. Findings from lung biopsy may aid decision making in selected patients as a part of a step-wise diagnostic algorithm.

Differences in severity of cervical dysplasia between Ontario residents and refugees

Our study aims to compare the grade of cervical dysplasia by histology at initial presentation to colposcopy clinic between patients billing through Interim Federal Health Program (IFHP) ,as a proxy for refugee status, and patients billing through Ontario Health Insurance Plan (OHIP). We hypothesize that refugees present with a higher grade of dysplasia compared to Ontario residents.

Advanced Cervical Neoplasia Rates in Young Service Members: Implications of Primary HPV Screening for Military Readiness [ID: 1380248

INTRODUCTION: The new American Cancer Society (ACS) cervical cancer screening guidelines dissuade cervical cancer screening in women younger than 25, and may become universal national screening guidelines. We queried the incidence of advanced cervical dysplasia and carcinoma in military service members to determine the readiness implications of these recommendations. METHODS: A retrospective cohort study using the Military Health System (MHS) Data Repository and Management Analysis and Reporting Tool (MDR/M2) was performed to identify active-duty patients aged 21–25 diagnosed with cervical dysplasia and cancer across all military treatment facilities (MTFs) from January 1, 2017 to December 31, 2021. Additionally, patient age, human papillomavirus (HPV) infection status, and treatment type were collected. RESULTS: Only active-duty patients treated in a MTF fulfilling the above criteria were captured. In the 5 years of data collection, there were 955 active-duty women who met the inclusion criteria. Moderate to severe cervical dysplasia accounted for 62.3%, while carcinoma in situ and cervical cancer accounted for 35.6%, and 2.1%, respectively. The majority of patients did not have HPV testing or vaccination status encoded; therefore, this endpoint was eliminated from analysis. CONCLUSION: There are a militarily significant number of cases of advanced cervical lesions among young service members. If the new ACS guidelines are adopted, service members with treatable precancerous conditions will evade or delay detection, resulting in cancers that compromise readiness, increase cost, and compromise the health of military women. Mandatory HPV vaccination should be considered if ACS guidelines are adopted.

Morphological Assessment of the Temporomandibular Joint in Asymptomatic Brachycephalic Dogs Using Computed Tomography.

Temporomandibular joint (TMJ) incongruity and morphological variations can result in clinical signs but have also been reported in asymptomatic brachycephalic dogs. The purpose of this study was to assess TMJ morphology in a group of brachycephalic dogs using computed tomography (CT). French Bulldogs, English Bulldogs, Boxers, Cavalier King Charles Spaniels (CKCS), Chihuahuas, Lhasa Apsos, Pugs, Shih Tzus, and Staffordshire Bull Terriers were retrospectively enrolled. The severity of the TMJ morphological changes was determined using a modified 5-grade classification system. The intra- and inter-observer agreements were calculated. One hundred fifty-three dogs were included. When evaluating the medial aspect of the TMJ in the sagittal plane, there was a spectrum of variations in the shape of the head of the condylar process of the mandible, the mandibular fossa and the retroarticular process ranging from a rounded concave TMJ with a long retroarticular process to a flattened TMJ with an absent process. Variations in the articular surface of the head of the condyle in the transverse plane ranged from flat, through curved and trapezoid to sigmoid. The prevalence of severe TMJ dysplasia (grades B3 and C) in the CKCS and French Bulldog was high (69.2% and 53.8%, respectively). The intra- and inter-observer agreements were moderate. Variations in TMJ morphology exist in asymptomatic brachycephalic dogs. Marked changes seem to be highly prevalent in the French Bulldog and CKCS and should be considered a breed variation. The TMJ classification described in this study could be used to standardize assessment of canine TMJ morphology. However, further research is needed to determine its clinical application.

Respiratory Outcomes for Ventilator-Dependent Children With Bronchopulmonary Dysplasia.

To describe outpatient respiratory outcomes and center-level variability among children with severe bronchopulmonary dysplasia (BPD) who require tracheostomy and long-term mechanical ventilation. Retrospective cohort of subjects with severe BPD, born between 2016 and 2021, who received tracheostomy and were discharged on home ventilator support from 12 tertiary care centers participating in the BPD Collaborative Outpatient Registry. Timing of key respiratory events including time to tracheostomy placement, initial hospital discharge, first outpatient clinic visit, liberation from the ventilator, and decannulation were assessed using Kaplan-Meier analysis. Differences between centers for the timing of events were assessed via log-rank tests. There were 155 patients who met inclusion criteria. Median age at the time of the study was 32 months. The median age of tracheostomy placement was 5 months (48 weeks' postmenstrual age). The median ages of hospital discharge and first respiratory clinic visit were 10 months and 11 months of age, respectively. During the study period, 64% of the subjects were liberated from the ventilator at a median age of 27 months and 32% were decannulated at a median age of 49 months. The median ages for all key events differed significantly by center (P ≤ .001 for all events). There is wide variability in the outpatient respiratory outcomes of ventilator-dependent infants and children with severe BPD. Further studies are needed to identify the factors that contribute to variability in practice among the different BPD outpatient centers, which may include inpatient practices.

The Optimal State Scoring Tool: guidance for interdisciplinary care of infants with severe bronchopulmonary dysplasia and its relation to linear growth.

Infants with severe bronchopulmonary dysplasia (sBPD) have complex medical courses. We developed the clinician-rated Optimal State Scoring Tool (OSST) that measures factors relevant to clinical improvement of sBPD and investigated preliminary validity using linear growth outcome and OSST scores in sBPD patients. Tool development process and pilot findings are provided for 13 patients evaluated longitudinally. OSST scores, length measurements, and steroid dependency values were obtained. Changes in OSST scores and lengths were examined using linear mixed-effect models. OSST scores were significantly correlated with linear growth (95% CI 0.36, 0.57). The steroid-dependent group showed significantly slower rate of linear growth (95% CI 0.74, 1.05) and slower rate of increase in OSST scores (95% CI 0.99, 2.13) compared to the non-steroid-dependent group, with the OSST showing the largest effect size. Pilot data reflect promising evidence for OSST construct validity in monitoring clinical outcomes in sBPD patients.

Relationship between Ventricular Size on Latest Ultrasonogram and the Bayley Scores ≥ 18 Months in Extremely Low Gestational Age Neonates: A Retrospective Cohort Study.

A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) in preterm infants with birth weight <1,250 g. However, VBI obtained at the third ventricle has only moderate interobserver reliability. The objective of this study was to test (1) reliability of VBI measured at the foramen of Monro on the latest ultrasonogram (US) before discharge using the intraclass correlation coefficient (ICC) and (2) the relationship between VBI and BSID-III scores at ≥18 months corrected age. The present study is a single-center retrospective cohort study. The study included 270 preterm infants born at 230/7 to 286/7 weeks of gestational age. The ICC of VBI between independent measurements by two study radiologists on the first 50 patients was 0.934. Factors associated with the value of VBI included severe intraventricular hemorrhage, bronchopulmonary dysplasia, and systemic steroid administration for BPD but not postmenstrual age. In multivariate analysis, VBI was negatively and independently associated with cognitive (p = 0.002), language (p = 0.004), and motor (p < 0.001) BSID-III scores. The association between VBI and BSID-III scores was observed even in infants in whom the latest US was obtained before term equivalent age. The association between VBI and BSID-III scores was also observed after excluding those with severe intraventricular hemorrhage. In this very preterm cohort the measurement of VBI had excellent reliability. Moreover, VBI measurements were negatively associated with motor, language, and cognitive BSID-III scores. · Mean values of VBI are stable with postmenstrual age.. · Values at the foramen of Monro are reliable and reproducible.. · VBI is negatively associated with Bayley scores.. · The association is observed even before term age..