Specific Diagnosis Research Articles

Nuclear DUX4 immunohistochemistry is a highly sensitive and specific marker for the presence of CIC::DUX4 fusion in CIC-rearranged sarcomas: a study of 48 molecularly confirmed cases.

CIC-rearranged sarcomas (CRS) are clinically aggressive undifferentiated round cell sarcomas (URCS), commonly driven by CIC::DUX4. Due to the repetitive nature of DUX4 and the variability of the fusion breakpoints, CIC::DUX4 fusion may be missed by molecular testing. Immunohistochemical (IHC) stains have been studied as surrogates for the CIC::DUX4 fusion. We aim to assess the performance of DUX4 IHC in the work-up of CRS and its expression in non-CRS round cell or epithelioid neoplasms. Cases of molecularly confirmed CRS (n = 48) and non-CRS (n = 105) were included. CRS cases consisted of 35 females and 13 males, with ages ranging from less than 1 year to 67 years (median = 41 years). Among the molecularly confirmed non-CRS cases, C-terminal DUX4 expression was investigated in Ewing sarcomas (38 cases), alveolar rhabdomyosarcomas (18 cases), desmoplastic smallround cell tumours (12 cases) and synovial sarcomas (n = five), as well as in non-mesenchymal neoplasms such as SMARCA4/SMARCB1-deficient tumours (n = five), carcinomas of unknown primary (n = three) and haematolymphoid neoplasms (four cases). DUX4 IHC was considered positive when strong nuclear expression was detected in more than 50% of neoplastic cells. When used as a surrogate for the diagnosis of CRS, the sensitivity and specificity of DUX4 IHC was 98 and 100%, respectively. Only one CRS case was negative for DUX4 IHC and harboured a CIC::FOXO4 fusion. DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS.

Can ultrasound elastography be useful in the diagnosis of poor ovarian response?

This study aims to compare the elastographic properties of the ovaries of patients with poor ovarian response (POR) with healthy controls by using real-time ultrasound tissue elastography and to investigate the predictive value of ovarian strain ratio (OSR) in the diagnosis of POR. A cross-sectional study was conducted among infertility patients. OSR measurements of 46 women diagnosed with POR and 41 healthy controls with male infertility were performed by real-time ultrasound tissue elastography. Ovarian volume, OSR, antral follicle count (AFC), age, body mass index (BMI), anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), and estradiol (E2) values, were compared between the groups. A receiver operating characteristic curve was used to compare the sensitivity and specificity of OSR, AFC, AMH, FSH, and E2 for POR diagnosis. Patients with POR were significantly older, had a lower duration of infertility, lower AMH, higher FSH, higher E2, lower AFC and ovarian volume (p < 0.01, p = 0.02, p < 0.01, p < 0.01, p < 0.01, p < 0.01, p < 0.01, respectively). The mean OSR of both ovaries was similar between the groups. For the diagnosis of POR, the sensitivity and specificity for AMH were 97.5% and 100%, for AFC were 86.7% and 97.6%; for FSH were 66.7% and 80.5%, for E2 were 53.3% and 90.2%, respectively. The significant independent predictors of the POR were AMH, AFC, and FSH, with no additional significant contribution from OSR. However, considering the relationship between POR and ovarian fibrosis, it is recommended to investigate this issue in more comprehensive studies.

Development and validation of an assay to quantify plasma cell-free human papillomavirus DNA for 13 high-risk types that cause 98% of HPV-positive cancers.

6065 Background: Plasma cell-free HPV DNA (cfHPV) may be a valuable tool for identification of patients with local-regionally advanced HPV-positive cancers at risk for recurrence after chemoradiation. Technical validation is required for use as an integral biomarker in a prospective clinical trial. Methods: Cell-Free 13 (i.e., CF13) is a digital-droplet PCR assay for quantification of 13 high-risk HPV types and control ERV3 in plasma that considered both variant sequences into primer/probe design and a distance matrix in phylogenetic analysis in multiplex combinations. Oligonucleotides/plasmids encoding type-specific E6/E7 regions were used as positive controls. Limit of blank, detection, quantification (LoB, LoD, LoQ), linear range, inter- and intra-assay coefficients of variation (CoV), and type-specific cross-reactivity were determined as were sensitivity and specificity for an HPV-positive diagnosis in a cohort of 278 oropharyngeal/unknown primary/oral cavity cancers tested for HPV by E6/E7 mRNA qRT-PCR or p16 IHC and HPV in situ hybridization. Results: Under identical assay conditions, the LoB, LoD and linear range were &lt;1, 5 and 5 to 200,000 virus copies without HPV type-specific cross-reactivity. Multiplexing had no effect on LoD or linearity. LoQ was 16 copies/ml plasma for all 13 HPV types. For 80 and 10,000 copies per ml, inter-assay CoV ranged from ~15-28% and ~3.2-4.6% and intra-assay CoV ranged from ~16-38% and 0.2-3.3%, respectively. cfDNA purification method (manual v automated; extraction efficiency 142% and 91% for 16 and 10,000 HPV16 copies/ml), input plasma volume (1, 2, or 4 ml), total background cfDNA (&lt;1800ng) or genomic DNA (&lt;700ng) did not affect quantification. For a diagnosis of HPV-positive cancer, sensitivity and specificity were 91.1% (214/235) and 97.7% (42/43), respectively. cfHPV was associated with gender, race, T stage, N stage, and primary treatment modality. When compared to below the median (≤230 copies/ml), cfHPV above the median was associated with worse progression-free survival (HR=2.26, 95% CI 1.23-4.17, p=0.009) in univariate analysis. However, this was no longer significant after adjustment for age, T stage, and M stage (HRadj=1.78, 95% CI 0.95-3.35, p=0.07). Conclusions: CF13 has high sensitivity, accuracy, precision, linearity, HPV type-specificity, and robustness, offering a rigorously validated assay applicable to ~98% of patients with HPV-positive cancer. CF13 had excellent clinical sensitivity and specificity for a diagnosis of HPV-positive OPC.

Idiopathic Pulmonary Fibrosis: From Common Microscopy to Single-Cell Biology and Precision Medicine.

Idiopathic pulmonary fibrosis is a chronic, progressive, and usually fatal lung disease of unknown etiology and is included in the large, complex, and heterogeneous group of interstitial lung diseases (ILD). IPF is characterized by an aberrant activation of epithelial cells and fibroblasts and excessive accumulation of extracellular matrix, resulting in the progressive destruction of the lung architecture. Here we approach the fascinating historical evolution of our knowledge about this disorder from the past century, when most efforts were focused on ILD classification and terminology, until the current century, when the explosive progress in molecular genetics, epigenetics, and multiomics, as well as the development of complex computational tools, resulted in a huge advance in unveiling the pathogenic mechanisms of the disease. Recent advances in artificial intelligence, machine and deep learning, and artificial neural networks show promising results in identifying lung fibrotic patterns in high-resolution computed tomography or helping to create a tissue genomic classifier for specific diagnosis. Finally, incipient approaches to precision medicine are ongoing in the area of pharmacogenetics.

Pathologically based criteria to distinguish essential tremor from controls: analyses of the human cerebellum.

Essential tremor is among the most prevalent neurological diseases. Diagnosis is based entirely on neurological evaluation. Historically, there were few postmortem brain studies, hindering attempts to develop pathologically based criteria to distinguish essential tremor from control brains. However, an intensive effort to bank essential tremor brains over recent years has resulted in postmortem studies involving >200 brains, which have identified numerous degenerative changes in the essential tremor cerebellar cortex. Although essential tremor and controls have been compared with respect to individual metrics of pathology, there has been no overarching analysis to derive a combination of metrics to distinguish essential tremor from controls. We asked whether there is a constellation of pathological findings that separates essential tremor from controls, and how well that constellation performs. Analyses included 100 essential tremor brains from the essential tremor centralized brain repository and 50 control brains. A standard tissue block from the cerebellar cortex was used to quantify 11 metrics of pathological change. Three supervised classification algorithms were investigated, with data divided into training and validation samples. Using three different algorithms, we illustrate the ability to correctly predict a diagnosis of essential tremor, with sensitivity and specificity >87%, and in the majority of situations, >90%. We also provide a web-based application that uses these metric values, and based on specified cutoffs, determines the likely diagnosis. These analyses set the stage for use of pathologically based criteria to distinguish clinically diagnosed essential tremor cases from controls, at the time of postmortem.

Illumina and Nanopore sequencing in culture-negative samples from suspected lower respiratory tract infection patients.

To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis. Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.

Risk prediction and analysis of gallbladder polyps with deep neural network

The aim of this study is to analyze the risk factors associated with the development of adenomatous and malignant polyps in the gallbladder. Adenomatous polyps of the gallbladder are considered precancerous and have a high likelihood of progressing into malignancy. Preoperatively, distinguishing between benign gallbladder polyps, adenomatous polyps, and malignant polyps is challenging. Therefore, the objective is to develop a neural network model that utilizes these risk factors to accurately predict the nature of polyps. This predictive model can be employed to differentiate the nature of polyps before surgery, enhancing diagnostic accuracy. A retrospective study was done on patients who had cholecystectomy surgeries at the Department of Hepatobiliary Surgery of the Second People’s Hospital of Shenzhen between January 2017 and December 2022. The patients’ clinical characteristics, lab results, and ultrasonographic indices were examined. Using risk variables for the growth of adenomatous and malignant polyps in the gallbladder, a neural network model for predicting the kind of polyps will be created. A normalized confusion matrix, PR, and ROC curve were used to evaluate the performance of the model. In this comprehensive study, we meticulously analyzed a total of 287 cases of benign gallbladder polyps, 15 cases of adenomatous polyps, and 27 cases of malignant polyps. The data analysis revealed several significant findings. Specifically, hepatitis B core antibody (95% CI −0.237 to 0.061, p < 0.001), number of polyps (95% CI −0.214 to −0.052, p = 0.001), polyp size (95% CI 0.038 to 0.051, p < 0.001), wall thickness (95% CI 0.042 to 0.081, p < 0.001), and gallbladder size (95% CI 0.185 to 0.367, p < 0.001) emerged as independent predictors for gallbladder adenomatous polyps and malignant polyps. Based on these significant findings, we developed a predictive classification model for gallbladder polyps, represented as follows, Predictive classification model for GBPs = −0.149 * core antibody − 0.033 * number of polyps + 0.045 * polyp size + 0.061 * wall thickness + 0.276 * gallbladder size − 4.313. To assess the predictive efficiency of the model, we employed precision-recall (PR) and receiver operating characteristic (ROC) curves. The area under the curve (AUC) for the prediction model was 0.945 and 0.930, respectively, indicating excellent predictive capability. We determined that a polyp size of 10 mm served as the optimal cutoff value for diagnosing gallbladder adenoma, with a sensitivity of 81.5% and specificity of 60.0%. For the diagnosis of gallbladder cancer, the sensitivity and specificity were 81.5% and 92.5%, respectively. These findings highlight the potential of our predictive model and provide valuable insights into accurate diagnosis and risk assessment for gallbladder polyps. We identified several risk factors associated with the development of adenomatous and malignant polyps in the gallbladder, including hepatitis B core antibodies, polyp number, polyp size, wall thickness, and gallbladder size. To address the need for accurate prediction, we introduced a novel neural network learning algorithm. This algorithm utilizes the aforementioned risk factors to predict the nature of gallbladder polyps. By accurately identifying the nature of these polyps, our model can assist patients in making informed decisions regarding their treatment and management strategies. This innovative approach aims to improve patient outcomes and enhance the overall effectiveness of care.

Assessing the effectiveness and safety of transbronchial lung cryobiopsy utilizing a flexible bronchoscope with an endobronchial blocker in diffuse parenchymal lung lesions.

Transbronchial lung cryobiopsy (TBLC) with flexible bronchoscope represents an encouraging modality to obtain a larger size specimen without crush artifact, and a higher diagnostic yield in patients with diffuse parenchymal lung lesions/diseases as compared to conventional transbronchial lung biopsy, and fewer complications as opposed to surgical lung biopsy. Artificial airway is preferred as it provides better airway protection in cases of severe bleeding. Although various researchers have published data on different modalities, the data is not sufficient to standardize a single technique. This study describes the procedural technique, safety, and yield of TBLC using a flexible bronchoscope with an endobronchial blocker. We performed a retrospective analysis of 100 consecutive patients who underwent TBLC using flexible bronchoscopy from May 2018 to June 2022. TBLC samples were obtained under moderate sedation without the use of artificial airway or fluoroscopy. Among the 100 patients, the majority were male (63%). The mean age of the enrolled patients was 44.43±15.92 years. The predominant diagnoses in our study were hypersensitivity pneumonitis (27%), followed by sarcoidosis (12%) and tuberculosis (10%). We obtained alveolated lung tissue in 90 out of 100 cases with a median biopsy size of 5 mm (in greatest dimension, interquartile range 5-4 mm), resulting in a specific histopathological diagnosis in 82 cases. The most frequent complications were bleeding and pneumothorax (13%). Mild bleeding occurred in 58% of the patients, and moderate bleeding occurred in 20% of the patients. There was no episode of severe/life-threatening bleeding. None of the patients required intensive care unit admission or endotracheal intubation. In conclusion, the use of TBLC through flexible bronchoscopy with an endobronchial blocker emerges as a minimally invasive, secure, time-efficient, and readily reproducible technique. Significantly, this procedure can be seamlessly executed in the bronchoscopy suite, eliminating the requirement for an artificial airway or general anesthesia.

Infertility and risk of postmenopausal breast cancer in the women's health initiative.

Although infertility (i.e., failure to conceive after ≥ 12months of trying) is strongly correlated with established breast cancer risk factors (e.g., nulliparity, number of pregnancies, and age at first pregnancy), its association with breast cancer incidence is not fully understood. Previous studies were primarily small clinic-based or registry studies with short follow-up and predominantly focused on premenopausal breast cancer. The objective of this study was to assess the relationship between infertility and postmenopausal breast cancer risk among participants in the Women's Health Initiative (analytic sample = 131,784; > 25years of follow-up). At study entry, participants were asked about their pregnancy history, infertility history, and diagnosed reasons for infertility. Incident breast cancers were self-reported with adjudication by trained physicians reviewing medical records. Cox proportional hazards models were used to estimate risk of incident postmenopausal breast cancer for women with infertility (overall and specific infertility diagnoses) compared to parous women with no history of infertility. We examined mediation of these associations by parity, age at first term pregnancy, postmenopausal hormone therapy use at baseline, age at menopause, breastfeeding, and oophorectomy. We observed a modest association between infertility (n = 23,406) and risk of postmenopausal breast cancer (HR = 1.07; 95% CI 1.02-1.13). The association was largely mediated by age at first term pregnancy (natural indirect effect: 46.4% mediated, CI 12.2-84.3%). These findings suggest that infertility may be modestly associated with future risk of postmenopausal breast cancer due to age at first pregnancy and highlight the importance of incorporating reproductive history across the life course into breast cancer analyses.

Abstract A042: History of infertility and risk of ovarian cancer in the women’s health initiative

Abstract Background: Given the consistent relationship between reproductive factors (e.g. parity) and risk of epithelial ovarian cancer, several studies have investigated the relation between infertility and ovarian cancer with conflicting results. Prior research has suggested differences in risk by specific infertility subgroups, which may have contributed to the conflicting findings. Further, few studies examined associations by ovarian cancer histotypes or were able to disentangle the influence of infertility vs. fertility treatment. Differences across studies could also have been influenced by different study populations (e.g., population-based vs. clinical population/registry of in-vitro fertilization [IVF]) and lack of consistent statistical control for important confounding factors including nulliparity, number of pregnancies, and age at first pregnancy. Finally, prior prospective studies have had limited follow-up, thus not capturing cancers that occur after menopause and which may have different risk factor profiles. Our objective was to determine the association between history of infertility and risk of postmenopausal ovarian cancer in a population that had not received treatment with IVF. Methods: We utilized the Women’s Health Initiative (n=114,761) with over 25 years of follow-up. At study baseline participants were asked whether they had ever tried to become pregnant for more than one year without becoming pregnant and whether a reason was found. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of incident ovarian cancer comparing participants with a history of infertility to parous participants without infertility. Logistic regression models were used to calculate odds ratios (OR) for prevalent ovarian cancer at study baseline. Results: Approximately 16% of participants reported a history of infertility. 1,376 participants reported prevalent ovarian cancer at study baseline and 852 cases of ovarian cancer were diagnosed during study follow-up. In the prospective analyses, no statistically significant association was observed between infertility and risk of ovarian cancer overall (HR=1.16; 95% CI=0.98-1.37), by histotype, or with any specific infertility diagnoses. When prevalent ovarian cancer was examined, those reporting a history of infertility had a greater odds of ovarian cancer diagnosis (1.34; 95% CI=1.13-1.58) at WHI cohort baseline. This association was present for most infertility diagnoses with the strongest associations for hormonal/ovulatory (OR=1.97;95% CI=1.24-3.12), tubal/uterine factor (OR=1.63; 95% CI=1.15-2.31), and male factor (OR=1.71; 95% CI=1.19-2.47) infertility. Conclusions: We observed no significant association between infertility history and incident ovarian cancer in our population of postmenopausal participants. An association between infertility and ovarian cancer was present when prevalent ovarian cancer cases were examined, consistent with prior analyses that show stronger associations between ovarian cancer risk factors and ovarian cancer among younger women. Citation Format: Holly Harris, Kimberly Lind, Cynthia Thomson, Nazmus Saquib, Aladdin Shadyab, Peter Schnatz, Rogelio Robles-Morales, Lihong Qi, Howard Strickler, Denise Roe, Leslie Farland. History of infertility and risk of ovarian cancer in the women’s health initiative [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A042.

Differences in Baseline Physical Function and Mental Health PROM Scores in Patients With Foot and Ankle Conditions.

This study sought to establish normative values for baseline physical and mental health by foot and ankle diagnosis using validated PROMIS scores and to compare the correlation between these 2 outcomes across common diagnoses. Additionally, it investigated the effects associated with chronic vs acute conditions and specific diagnoses on mental health. We reviewed baseline PROMIS Physical Function 10a (PF10a) and PROMIS Global-Mental (PGM) scores of 14,245 patients with one of the 10 most common foot and ankle diagnoses seen at our institution between 2016 and 2021. Pearson correlation coefficients were calculated to assess the relationship between PF10a and PGM by diagnosis. A multivariable regression model including age, sex, language, race, ethnicity, education level, income, and Charlson Comorbidity Index was used to determine the associated effect of diagnosis on PGM score. On unadjusted analysis, patients diagnosed with an ankle fracture had the lowest mean physical function, whereas patients with hallux valgus had the highest (PF10a = 33.9 vs 46.7, P < .001). Patients with foot/ankle osteoarthritis had the lowest mean self-reported mental health, whereas patients with hallux rigidus had the highest (PGM = 49.9 vs 53.4, P < .001). PF10a and PGM scores were significantly positively correlated for all diagnoses; the correlation was strongest in patients diagnosed with foot/ankle osteoarthritis or hammertoes (r = 0.511) and weakest in patients with ankle fractures (r = 0.232) or sprains (r = 0.280). Chronic conditions, including hammertoes (β = -5.1, 95% CI [-5.8, -4.3], P < .001), foot/ankle osteoarthritis (β = -5.0, 95% CI [-5.7, -4.3], P < .001), and hallux valgus (β = -4.8, 95% CI [-5.5, -4.1], P < .001) were associated with the largest negative effects on patients' mental health. Self-reported physical function and mental health varied across common foot and ankle diagnoses and were more tightly correlated in chronic conditions. The associations between diagnosis and mental health scores appear larger for more chronic diagnoses, including those that are generally associated with relatively unimpaired physical function. Level IV, retrospective, cross-sectional study.

March 2024 Pulmonary Case of the Month: A Nodule of a Different Color

No abstract available. Article truncated after 150 words. History of Present Illness The patient is a 73-year-old woman from Wisconsin seen in January 2024 for lung nodules. She had been followed by her physician in Wisconsin for lung nodules but had never had a biopsy or specific diagnosis. She reported that the nodules “waxed and waned.” Her Wisconsin physician suggested she be evaluated in Arizona. She has occasional cough attributed to paroxysmal nocturnal dyspnea, but denies sputum production, fever, chills or shortness of breath Past Medical History, Family History and Social History • Rheumatoid arthritis diagnosed in her 30s, although not currently on any treatment. • Breast cancer 2006, treated with chemoradiation • Osteoporosis • Family history: negative for lung cancer or other lung disorders • Social History: Lifelong nonsmoker Medications • None Physical Examination • Unremarkable Laboratory • Normal CBC • Cocci serology: negative • Rheumatoid factor: elevated 61 U/ml (normal &lt; 15) • Anti-cyclic citrullinated peptide antibody: negative • Erythrocyte Sedimentation Rate: normal Radiology A thoracic CT of …

Diverse retinal-kidney phenotypes associated with NPHP1 homozygous whole-gene deletions in patients with kidney failure

A precise diagnosis in medicine allows appropriate disease-specific management. Kidney failure of unknown aetiology remains a frequent diagnostic label within the haemodialysis unit and kidney transplant clinic, accounting for 15–20% of these patients. Approximately 10% of such cases may have an underlying monogenic cause of kidney failure. Modern genetic approaches can provide a precise diagnosis for patients and their families. A search for extra-renal disease manifestations is also important as this may point to a specific genetic diagnosis. Here, we present two patients where molecular genetic testing was performed because of kidney failure of unknown aetiology and associated retinal phenotypes. The first patient reached kidney failure at 16 years of age but only presented with a retinal phenotype at 59 years of age and was found to have evidence of rod-cone dystrophy. The second patient presented with childhood kidney failure at the age of 15 years and developed visual difficulties and photophobia at the age of 32 years and was diagnosed with cone dystrophy. In both cases, genetic tests were performed which revealed a homozygous whole-gene deletion of NPHP1-encoding nephrocystin-1, providing the unifying diagnosis of Senior-Løken syndrome type 1. We conclude that reviewing kidney and extra-renal phenotypes together with targeted genetic testing was informative in these cases of kidney failure of unknown aetiology and associated retinal phenotypes. The involvement of an interdisciplinary team is advisable when managing such patients and allows referral to other relevant specialities. The long time lag and lack of diagnostic clarity and clinical evaluation in our cases should encourage genetic investigations for every young patient with unexplained kidney failure. For these and similar patients, a more timely genetic diagnosis would allow for improved management, a risk assessment of kidney disease in relatives, and the earlier identification of extra-renal disease manifestations.

Associations of Mental Health Service Utilization and Mental Health Diagnosis with Placement Instability Among Foster Children in a Southeastern State

AbstractPlacement instability for children in foster care is high, with children experiencing nearly 4.5 placement moves per 1,000 days in care on average. While prior research has demonstrated a predictive relationship between mental health problems and placement instability, few studies have examined the associations of specific mental health diagnoses or utilization of mental health (MH) services. To this end, this study seeks to investigate associations between MH service utilization, mental health diagnosis, and placement instability (rate of placement moves) for foster children. We analyzed statewide integrated administrative data to examine MH service utilization and mental health diagnosis on placement instability among foster children. We used SAS 9.4 to conduct descriptive, bivariate, and multiple linear regression models to address the objectives of the study. The retrospective cohort was composed of 1,002 children in foster care. The multivariable linear regression reveals that receiving in-patient services, receiving out-patient services, being diagnosed with conduct disorder, being Black children, older children, and female children, being placed in intensive case management, being sexually abused, having a single household family structure at time of removal, and having a high number of intakes significantly increased the rate of placement moves. The findings of this study have significant implications for the provision of mental health services to foster children and the promotion of placement stability, highlighting the role of child welfare professionals in fostering protective factors and mitigating risk factors to promote placement stability. Implications for practice and policy improvement are discussed.

Predictors of non-fatal suicide attempts among Veterans Health Administration (VHA) patients who experienced military sexual trauma.

Military sexual trauma (MST) has been identified as a risk factor for suicidal behavior. To inform suicide prevention efforts within the Veterans Health Administration (VHA), this study evaluates predictors of non-fatal suicide attempts (NFSAs) among VHA patients who experienced MST. For VHA patients in fiscal year (FY) 2019 who previously screened positive for a history of MST, documented NFSAs were assessed. Using multivariable logistic regression, demographic, clinical, and VHA care utilization predictors of NFSAs were assessed. Of the 212,215 VHA patients who screened positive for MST prior to FY 2019 and for whom complete race, service connection, and rurality information was available, 1742 (0.8%) had a documented NFSA in FY 2019. In multivariable logistic regression analyses, total physical and mental health morbidities were not associated with NFSA risk. Predictors of a documented NFSA included specific mental health diagnoses [adjusted odds ratio (aOR) range: 1.28-1.94], receipt of psychotropic medication prescriptions (aOR range: 1.23-2.69) and having a prior year emergency department visit (aOR = 1.32) or inpatient psychiatric admission (aOR = 2.15). Among VHA patients who experienced MST, specific mental health conditions may increase risk of NFSAs, even after adjustment for overall mental health morbidity. Additionally, indicators of severity of mental health difficulties such as receipt of psychotropic medication prescriptions and inpatient psychiatric admissions are also associated with increased risk above and beyond risk associated with diagnoses. Findings highlight targets for suicide prevention initiatives among this vulnerable group within VHA and may help identify patients who would benefit from additional support.

Speech and language in DDX3X-neurodevelopmental disorder: A call for early augmentative and alternative communication intervention.

Pathogenic variants in DDX3X are associated with neurodevelopmental disorders. Communication impairments are commonly reported, yet specific speech and language diagnoses have not been delineated, preventing prognostic counseling and targeted therapies. Here, we characterized speech and language in 38 female individuals, aged 1.69-24.34 years, with pathogenic and likely pathogenic DDX3X variants (missense, n = 13; nonsense, n = 12; frameshift, n = 7; splice site, n = 3; synonymous, n = 2; deletion, n = 1). Standardized speech, language, motor, social, and adaptive behavior assessments were administered. All participants had gross motor deficits in infancy (34/34), and fine motor deficits were common throughout childhood (94%; 32/34). Intellectual disability was reported in 86% (24/28) of participants over 4 years of age. Expressive, receptive, and social communication skills were, on average, severely impaired. However, receptive language was significantly stronger than expressive language ability. Over half of the assessed participants were minimally verbal (66%; 22/33; range = 2 years 2 months-24 years 4 months; mean = 8 years; SD = 6 years) and augmented speech with sign language, gestures, or digital devices. A quarter of the cohort had childhood apraxia of speech (25%; 9/36). Despite speech and language impairments, social motivation was a relevant strength. Many participants used augmentative and alternative communication (AAC), underscoring the need for early, tailored, and comprehensive AAC intervention.

Characterizing Chronic Pain and Adverse Childhood Experiences in the Lesbian, Gay, Bisexual, Transgender, or Queer Community.

Childhood adversity is associated with chronic pain in adulthood. Additionally, individuals identifying as lesbian, gay, bisexual, transgender, or queer (LGBTQ+) report a greater prevalence of chronic pain and increased adverse childhood experiences (ACEs). While the LGTBQ+ community has a disproportionately high chronic disease burden, limited research has been conducted on the associations between chronic pain conditions or intensity and childhood adversity in this population. In this cross-sectional study, participants were 18 years or older, LGBTQ+ identifying, and reported chronic pain. Surveys were electronically distributed from August to November 2022 via LGBTQ+ organization email listservs and social media platforms. The survey included demographics and validated questionnaires measuring chronic pain (The Chronic Pain Questionnaire) and childhood adversity (ACE score). In analysis, ACE scores of 4 or more were defined as high. Responses from 136 individuals (average age of 29 ± 7.4 years) were analyzed. The mean for participants' average pain rating in the last 6 months was 5.9 of 10. Participants' worst pain was rated at least a 7 of 10 for 80% of respondents. Half (47%) had high ACE scores, and high ACE scores were significantly associated with higher average pain scores (6.27 ± 1.79, mean difference = -2.22, P = .028, 95% confidence interval [CI], -1.2 to -0.0), and higher perceived current pain ratings (4.53 ± 2.16, mean difference = -2.78, P = .007, 95% CI, -1.9 to -0.3). Transgender and gender diverse (TGD) participants (n = 75) had higher ACE scores (3.91 ± 1.78) and current pain scores compared to cisgender individuals (3.9 ± 1.8 vs 3.0 ± 1.9, P = .009, 95% CI, 0.0-0.3). History of any sexual trauma was prevalent in 36.7% and was associated with chronic pain located in the pelvic region ( P = .016, effect size estimate 0.21). Specific histories of forced sexual and touch encounters were associated with a specific diagnosis of fibromyalgia ( P = .008, effect size estimate 0.31 and P = .037, effect size estimate 0.31, respectively). Childhood adversity and chronic pain's dose-dependent relationship among our LGBTQ+ sample indicates a need to explore trauma's role in perceived pain. Given sexual trauma's association with pain location and diagnosis, type of trauma may also be crucial in understanding chronic pain development. Research into the relationships between childhood adversity, sexuality, gender identity, and chronic pain could improve chronic pain prevention and management for the LGBTQ+ community.

An unexpected case of a dog from Poland co-infected with Dirofilaria repens and Dirofilaria Immitis.

Dirofilariasis is a vector-borne disease caused by parasitic nematodes of the genus Dirofilaria spp., considered an emerging concern in both veterinary and human medicine. Climate changes and human activities, such as pet travel, contribute to the spread of diseases to new non-endemic regions. Poland is dominated by subcutaneous dirofilariasis caused by D. repens infections. Cardiopulmonary dirofilariasis, also known as a heartworm disease is much more rare with only single autochthonous cases reported so far. Also, imported infections are observed sporadically in dogs traveling to endemic countries. In this study, we report the first case of a dog in Poland, never having traveled abroad, co-infected with Dirofilaria repens and Dirofilaria immitis. A 14-year-old mixed breed, an intact male dog with fever, lightly pale mucosal membranes, moderate abdominal pain, and a mild cough was presented in a veterinary clinic in Warsaw, Poland. The examination of the blood sample collected for complete morphology and biochemistry revealed the presence of live microfilariae. Presence of the DNA of both microfilariae species was detected using Real-Time PCR with species-specific primers. Since the remaining diagnostic methods like Knott's test, antigen test or echocardiography did not reveal the presence of D. immitis, we discussed the impact of microfilariae periodicity and low worm burden infections on the limited efficiency of these techniques. We strongly recommend using a mixed diagnostic approach for the most sensitive and specific diagnosis since the ideal diagnostic method does not exist, and several factors may contribute to misdiagnosis. Furthermore, we considered factors that contribute to the uncontrolled spread of dirofilariasis such as climate changes, introduction of new species of mosquitoes competent for the transmission of the disease, and wildlife animals as an important reservoir of this parasitosis. Given that Poland shares borders with countries classified as endemic and pre-endemic for D. immitis, such as Slovakia and Ukraine, it is reasonable to anticipate a rise in autochthonous heartworm infections and shifts in the epidemiological pattern of dirofilariasis in the coming years.

Consensus-Based Development of a Pediatric Echocardiography Complexity Score: Design, Rationale, and Results of a Quality Improvement Collaborative.

The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score. The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. Univariate and multivariate analyses were performed to assess for independent predictors of longer study duration. Among the 174 echocardiograms analyzed, 68.9% had underlying congenital heart disease; 44.8% were outpatient; 34.5% were performed in an intensive care setting; 61.5% were follow-up; 46.6% were initial or preoperative; and 9.8% were sedated. All studies had an assigned PEC score. In univariate analysis, longer study duration was associated with several patient and study variables (age <2 years, PEC 4 or 5, initial study, preoperative study, junior or trainee scanner, and need for additional imaging). In multivariable analysis, a higher PEC score of 4 or 5 was independently associated with longer study duration after controlling for study variables and center variation. The PEC scoring tool is feasible and applicable in a variety of clinical settings and can be used for correlation with diagnostic errors, allocation of resources, and assessment of physician and sonographer effort in performing, interpreting, and training in pediatric echocardiography.

Feline dermatoses at Ferdowsi University of Mashhad (Iran): 154 cases (2009-2020).

Studies indicate that 6% to 20% of feline patients have at least one dermatopathy. This retrospective study aimed to provide comprehensive information about the types of skin diseases, diagnosis methods, treatments and follow-up data in a hospital population of domestic cats in Iran. The present survey of clinical observations was conducted on the medical records of 1825 individual cats brought to the Faculty of Veterinary Medicine, Ferdowsi University of Mashhad (Iran) over a 12-year period (2009-2020). Feline dermatoses accounted for 154 (8.43%) of the 1,825 cats examined during the study period. The most prevalent dermatological manifestations in the studied population of 154 were erythema, macules, papules and/or pustules (36; 23.37%), alopecia (18; 11.68%) and erosive/ulcerative lesions (17; 11.03%). Specific dermatological diagnoses made were the following (in descending order, of 154): dermatophytosis (34; 22.07%), subcutaneous abscesses (16; 10.38%), atopic skin syndrome/environmental allergies (20; 10.38%), external parasites (15; 9.74%), otitis (10; 6.49%), flea infestation (6; 3.89%), food allergy (4; 2.59%) and primary pyoderma (2; 1.29%). Most lesions were observed in the head/face of cats (41 of 154; 26.62%) and their ears (39; 25.32%). Following treatment, 86 of 154 cats (69.35%) had complete remissions, 17 cats faced recurrent dermatoses and the owners of 21 cats were not satisfied. The prevalence of dermatoses among this cohort of Iranian cats is similar to that in other parts of the world. However, a noticeable difference was detected in the most prevalent dermatoses. To the best of our knowledge, this is the first study to assess the characteristics and outcomes of feline dermatological conditions in Iran.