Quantitative DNA Methylation Analysis and Epigenotype-Phenotype Correlations in Taiwanese Patients with Silver-Russell Syndrome.

Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19-associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients.

[Clinical diagnosis of group A streptococcal pharyngitis and progress in the application of scoring systems]. / A族链球菌咽炎的临床诊断及评分制的应用进展.

Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.

Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology.

BACKGROUND: Recently, a patient with maternal uniparental disomy of chromosome 16 (UPD(16)mat) presenting with Silver-Russell syndrome (SRS) phenotype was reported. SRS is characterised by growth failure and dysmorphic features. OBJECTIVE: To clarify the prevalence of UPD(16)mat in aetiology-unknown patients with SRS phenotype and phenotypic differences between UPD(16)mat and SRS. METHODS: We studied 94 patients with SRS phenotype of unknown aetiology. Sixty-three satisfied the Netchine-Harbison clinical scoring system (NH-CSS) criteria, and 25 out of 63 patients showed both protruding forehead and relative macrocephaly (clinical SRS). The remaining 31 patients met only three NH-CSS criteria, but were clinically suspected as having SRS. To detect UPD(16)mat, we performed methylation analysis for the ZNF597:TSS-differentially methylated region (DMR) on chromosome 16 and subsequently performed microsatellite, SNP array and exome analyses in the patients with hypomethylated ZNF597:TSS-DMR. RESULTS: We identified two patients (2.1%) with a mixture of maternal isodisomy and heterodisomy of chromosome 16 in 94 aetiology-unknown patients with SRS phenotype. Both patients exhibited preterm birth and prenatal and postnatal growth failure. The male patient had ventricular septal defect and hypospadias. Whole-exome sequencing detected no gene mutations related to their phenotypes. CONCLUSION: We suggest considering genetic testing for UPD(16)mat in SRS phenotypic patients without known aetiology.

Effect of resistance exercise on peripheral neuropathy in Type 2 diabetes mellitus. / 抗阻力运动对2åž‹ç³–å°¿ç— å‘¨å›´ç¥žç»ç— å˜çš„å½±å“.

OBJECTIVES: To explore the improvement of neurological symptoms in patients with Type 2 diabetic peripheral neuropathy via resistance exercise. METHODS: A total of 100 patients with Type 2 diabetic peripheral neuropathy were selected as the research objects, and they were randomly divided into an observation group who performed resistance exercise (n=50) and a control group who did not performed resistance exercise (n=50). Resistance exercise was performed on the bioDensity™ resistance exercise instrument. The study graded the severity of diabetic peripheral neuropathy by the Toronto clinical scoring system (TCSS), and the improvement of diabetic peripheral neuropathy (DPN) was evaluated by the decline of the TCSS score. The observation group was treated with resistance exercise for 6 months. The changes of body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1C), total cholesterol (TC), glycerin trilaurate (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), and TCSS score were compared between baseline and 3, 6 months of exercise. At the same time, the differences in sensory test scores, nerve reflex scores, and neurological symptom scores were compared between the baseline, 3 and 6 months, in the observation group. Except for resistance exercise, the other treatments in the control group were the same as those in the observation group. RESULTS: Compared with the control group, there was statistically difference in the TCSS scores in the observation group at 3 months (P<0.05); there were also statistically difference in the HbA1C and TCSS scores in the observation group at 6 months (both P<0.05). The changes of TCSS scores, FBG, HbA1C in the observation group at 3 months and 6 months were significantly lower than those in the baseline, with significant differences (all P<0.05); but there were no significant differences in BMI, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure and TC, TG, LDL, HDL (all P>0.05). In the TCSS scores, the neurosymptom score, sensory test score were all reduced compared with the baseline, with significant differences (both P<0.05); but there was no significant difference in the neuroreflex score (P>0.05). In the control group, the TG and TC at 3 and 6 months were decreased compared with the baseline, and there was significant difference (both P<0.05), while there was no significant difference in the other indicators (all P>0.05). CONCLUSIONS: After the intervention of resistance exercise, the blood glucose and DPN can be improved in a certain extent, and which can be popularized in Type 2 diabetes patients.

Patient Predictors of Surgical Candidacy in Elective Spine Disorders.

BACKGROUND: The expansion of age-related degenerative spine pathologies has led to increased referrals to spine surgeons. However, the majority of patients referred for surgical consultation do not need surgery, leading to inefficient use of healthcare resources. This study aims to elucidate preoperative patient variables that are predictive of patients being offered spine surgery. METHODS: We conducted an observational cohort study on patients referred to our institution between May 2013 and January 2015. Patients completed a detailed preclinic questionnaire on items such as history of presenting illness, quality-of-life questionnaires, and past medical history. The primary end point was whether surgery was offered. A multivariable logistical regression using the random forest method was used to determine the odds of being offered surgery based on preoperative patient variables. RESULTS: An analysis of 1194 patients found that preoperative patient variables that reduced the odds of surgery being offered include mild pain (odds ratio [OR] 0.37, p=0.008), normal walking distance (OR 0.51, p=0.007), and normal sitting tolerance (OR 0.58, p=0.01). Factors that increased the odds of surgery include radiculopathy (OR 2.0, p=0.001), patient's belief that they should have surgery (OR 1.9, p=0.003), walking distance <50 ft (OR 1.9, p=0.01), relief of symptoms when bending forward (OR 1.7, p=0.008) and sitting (OR 1.6, p=0.009), works more slowly (OR 1.6 p=0.01), aggravation of symptoms by Valsalva (OR 1.4, p=0.03), and pain affecting sitting/standing (OR 1.1, p=0.001). CONCLUSIONS: We identified 11 preoperative variables that were predictive of whether patients were offered surgery, which are important factors to consider when screening outpatient spine referrals.

CONTEXTE: L'augmentation des pathologies de la colonne vertébrale liées au vieillissement de la population a entraîné un accroissement des cas de patients adressés à des chirurgiens spécialistes de la colonne vertébrale. Cela dit, la majorité de ces patients n'ont pas besoin d'une telle intervention chirurgicale, ce qui entraîne une utilisation inefficace des ressources prévues pour les soins de santé. Cette étude vise donc, en regard de ces patients, à déterminer les variables préopératoires susceptibles de prédire ceux à qui l'on offrira finalement une chirurgie de la colonne vertébrale. MÉTHODES: Nous avons réalisé une étude de cohorte observationnelle portant sur des patients ayant été acheminés vers notre établissement entre mai 2013 et janvier 2015. Ces patients ont tout d'abord complété un questionnaire préclinique détaillé abordant notamment les aspects suivants : les antécédents d'apparition de leur maladie, le fait d'avoir rempli auparavant des questionnaires portant sur leur qualité de vie et leurs antécédents médicaux. Le principal indicateur ici évalué a été dans quelle mesure une intervention chirurgicale fut offerte. À l'aide la méthode dite de « forêts des arbres décisionnels ¼ (random forest method), nous avons effectué une régression logistique à variables multiples afin de déterminer la probabilité qu'un patient se voit offrir une intervention chirurgicale. Pour ce faire, nous avons utilisé les variables préopératoires évoquées ci-dessus. RÉSULTATS: Parmi les 1194 patients analysés, nous avons déterminé qu'une douleur modérée (RC 0,37 ; p = 0,008), la capacité de parcourir à pied une distance normale (RC 0,51 ; p = 0,007) et la capacité normale de tolérer une position assise (RC 0,58 ; p = 0,01) étaient les variables préopératoires qui réduisaient la probabilité de se voir offrir une chirurgie. Parmi les variables augmentant au contraire la probabilité d'être acheminé vers un service de chirurgie, mentionnons les suivantes : être atteint de radiculopathie (RC 2,0 ; p = 0,001) ; le fait qu'un patient estime qu'il devrait bénéficier d'une opération chirurgicale (RC 1,9 ; p = 0,003) ; une capacité de marche inférieure à plus ou moins 15 mètres (50 pieds) (RC 1,9 ; p = 0,01) ; le soulagement des symptômes en se penchant vers l'avant (RC 1,7 ; p = 0,008) ou en s'asseyant (RC 1,6 ; p = 0,009) ; le fait de travailler plus lentement (RC 1,6 ; p = 0,01) ; l'aggravation des symptômes en lien avec la manœuvre de Valsalva (RC 1,4 ; p = 0,03) ; et des douleurs associées au fait de s'asseoir et de se lever (RC 1,1 ; p = 0,001). CONCLUSIONS: Au total, nous avons identifié 11 variables préopératoires qui peuvent nous aider à prédire dans quelle mesure des patients sont susceptibles de se voir offrir une intervention chirurgicale. Il est donc important d'en tenir compte au moment de sélectionner des patients externes ayant été acheminés vers un service de chirurgie en raison de troubles de la colonne vertébrale.

Development of a clinical scoring system for bovine respiratory disease in weaned dairy calves.

Clinical scoring systems for bovine respiratory disease (BRD) in weaned dairy calves have been developed in the past with calves experimentally infected with specific respiratory pathogens. In this prevalent case control study, a BRD clinical scoring system for weaned calves was developed using field data from 689 dairy calves housed in group pens on 5 dairies in California. Of the 689 calves in the study, 89 were selected because they appeared sick based on the display of lethargy, depression, or separation from the group, whereas the remaining 600 were randomly selected. Clinical signs were recorded for all calves, and BRD case status was determined by thoracic auscultation and ultrasound examinations, which were interpreted in parallel. Of the 689 calves, 238 were identified as BRD cases. Five survey-adjusted generalized linear mixed models with a logit link function, calf as the unit of analysis, and dairy as a random intercept were assessed using 3-fold cross-validation. The best model chosen based on performance and parsimony contained the variables cough (2 points), abnormal respiration (1 point), low body condition (5 points), sunken eyes (4 points), and a 24-h ambient temperature range >15°C (1 point) with a 2-point cutoff for a BRD suspect score. An alternative model did not contain a score for the covariate 24-h ambient temperature range and had a 1-point cutoff. The best model was tested on 174 observations not used for model training and resulted in 77.0% screening sensitivity, 100% diagnostic sensitivity, and 61.9% specificity. Adding rectal temperature ≥39.2°C (102.5°F) as a second-tier test increased specificity to 76.7% and lowered the screening sensitivity to 64.8% and diagnostic sensitivity to 76.9%. The alternative model had a screening sensitivity of 84.2%, diagnostic sensitivity of 100%, and specificity of 45.7%. Adding rectal temperature ≥39.2°C (102.5°F) as a second-tier test for score-positive animals improved specificity of the alternative model to 62.6% while lowering its screening sensitivity to 70.5% and diagnostic sensitivity to 76.9%. Use of a 2-tier California BRD postweaning scoring system may provide producers and veterinarians with a new tool to monitor BRD in group-housed dairy calves. Furthermore, the scoring system may aid in judicious medical intervention for BRD cases and reduce unnecessary treatments of animals with antimicrobials.

Development and validation of a new elbow-specific scoring system for patients with elbow stiffness: the Shanghai Elbow Dysfunction Score.

BACKGROUND: Clinical scoring systems are increasingly important and popular for the evaluation of orthopedic patients. Elbow stiffness commonly causes functional impairment and upper-limb disability. The purpose of this study was to develop and validate a new elbow-specific assessment score to evaluate joint function in patients with elbow stiffness. METHODS: The new system, the Shanghai Elbow Dysfunction Score (SHEDS), was developed in 3 portions: elbow motion capacities, elbow-related symptoms, and patient satisfaction level. A total of 73 patients with elbow stiffness were prospectively included. Intraclass correlation coefficients and Cronbach α values were calculated for test-retest reliability and internal consistency, respectively. Construct validity was assessed by correlating the SHEDS with previously validated scoring systems. Effect sizes (ES) and standardized response means (SRMs) were calculated for responsiveness. RESULTS: Positive reliability with an intraclass correlation coefficient of 0.83 and adequate homogeneity with a Cronbach α value of 0.74 were found for the SHEDS. Good to excellent validity using Spearman correlation coefficients (SCCs) were determined for the total (0.51-0.82), motion (0.65-0.89), and symptom (0.35-0.53) scores. Responsiveness was large for the total ES, 3.48; SRM, 2.96), motion (ES, 2.54; SRM, 2.08), and symptom (ES, 1.26; SRM, 1.14) scores. There were no ceiling or floor effects. Significant positive correlations were found between patient satisfaction levels and the final scores (SCC, 0.62), as well as the score changes of the SHEDS (SCC, 0.42). CONCLUSION: Our results suggest that the newly developed SHEDS is an excellent, comprehensive, valid scoring system to evaluate joint function in patients with elbow stiffness.

Development and Validation of a Chronic Pancreatitis Prognosis Score in 2 Independent Cohorts.

BACKGROUND & AIMS: The clinical course of chronic pancreatitis is unpredictable. There is no model to assess disease severity or progression or predict patient outcomes. METHODS: We performed a prospective study of 91 patients with chronic pancreatitis; data were collected from patients seen at academic centers in Europe from January 2011 through April 2014. We analyzed correlations between clinical, laboratory, and imaging data with number of hospital readmissions and in-hospital days over the next 12 months; the parameters with the highest degree of correlation were used to develop a 3-stage chronic pancreatitis prognosis score (COPPS). The predictive strength was validated in 129 independent subjects identified from 2 prospective databases. RESULTS: The mean number of hospital admissions was 1.9 (95% confidence interval [CI], 1.39-2.44) and 15.2 for hospital days (95% CI, 10.76-19.71) for the development cohort and 10.9 for the validation cohort (95% CI, 7.54-14.30) (P = .08). Based on bivariate correlations, pain (numeric rating scale), level of glycated hemoglobin A1c, level of C-reactive protein, body mass index, and platelet count were used to develop the COPPS system. The patients' median COPPS was 8.9 points (range, 5-14). The system accurately discriminated stages of disease severity (low to high): A (5-6 points), B (7-9), and C (10-15). In Pearson correlation analysis of the development cohort, the COPPS correlated with hospital admissions (0.39; P < .01) and number of hospital days (0.33; P < .01). The correlation was validated in the validation set (Pearson correlation values of 0.36 and 0.44; P < .01). COPPS did not correlate with results from the Cambridge classification system. CONCLUSIONS: We developed and validated an easy to use dynamic multivariate scoring system, similar to the Child-Pugh-Score for liver cirrhosis. The COPPS allows objective monitoring of patients with chronic pancreatitis, determining risk for readmission to hospital and potential length of hospital stay.

Relationship between ultrasonographic nerve morphology and severity of diabetic sensorimotor polyneuropathy.

BACKGROUND AND PURPOSE: In the current study, the aim was to characterize the nerve ultrasound cross-sectional areas (CSAs) of type 2 diabetic patients with diabetic sensorimotor polyneuropathy (DSP) of different severities. METHODS: A hundred symptomatic DSP patients and 40 age-matched healthy controls were prospectively recruited. DSP severity was ascertained through the Toronto Clinical Scoring System (TCCS). Nerve electrophysiology and ultrasound were performed on both lower limbs and the non-dominant upper limb. RESULTS: The sural nerve was inexcitable in 19.1% of mild, 40.0% of moderate and 69.0% of severe DSP groups. In contrast, CSAs were measurable in all nerves of DSP patients and were significantly larger compared to controls. Patients with severe DSP had significantly larger ulnar, peroneal, tibial and sural nerves compared to mild DSP patients. By receiver operating characteristic curve analysis, the cut-off value for the sural nerve at 2 mm(2) was a good discriminator (area under the curve 0.88) between the presence and absence of DSP (sensitivity 0.90; specificity 0.74) but performed less well in discriminating between the severity of DSP (cut-off 2.75 mm(2); area under the curve 0.62; sensitivity 0.59; specificity 0.73). Significant correlations were demonstrated between TCSS scores, most neurophysiology parameters and CSAs of the ulnar, peroneal, tibial and sural nerves. CONCLUSION: Nerve ultrasound in DSP reveals enlarged CSAs and these changes worsen with increasing disease severity, thus serving as a useful diagnostic tool especially when neurophysiology is unrevealing.

A prospective study validating a clinical scoring system and demonstrating phenotypical-genotypical correlations in Silver-Russell syndrome.

BACKGROUND: Multiple clinical scoring systems have been proposed for Silver-Russell syndrome (SRS). Here we aimed to test a clinical scoring system for SRS and to analyse the correlation between (epi)genotype and phenotype. SUBJECTS AND METHODS: Sixty-nine patients were examined by two physicians. Clinical scores were generated for all patients, with a new, six-item scoring system: (1) small for gestational age, birth length and/or weight ≤-2SDS, (2) postnatal growth retardation (height ≤-2SDS), (3) relative macrocephaly at birth, (4) body asymmetry, (5) feeding difficulties and/or body mass index (BMI) ≤-2SDS in toddlers; (6) protruding forehead at the age of 1-3 years. Subjects were considered to have likely SRS if they met at least four of these six criteria. Molecular investigations were performed blind to the clinical data. RESULTS: The 69 patients were classified into two groups (Likely-SRS (n=60), Unlikely-SRS (n=9)). Forty-six Likely-SRS patients (76.7%) displayed either 11p15 ICR1 hypomethylation (n=35; 58.3%) or maternal UPD of chromosome 7 (mUPD7) (n=11; 18.3%). Eight Unlikely-SRS patients had neither ICR1 hypomethylation nor mUPD7, whereas one patient had mUPD7. The clinical score and molecular results yielded four groups that differed significantly overall and for individual scoring system factors. Further molecular screening led identifying chromosomal abnormalities in Likely-SRS-double-negative and Unlikely-SRS groups. Four Likely-SRS-double negative patients carried a DLK1/GTL2 IG-DMR hypomethylation, a mUPD16; a mUPD20 and a de novo 1q21 microdeletion. CONCLUSIONS: This new scoring system is very sensitive (98%) for the detection of patients with SRS with demonstrated molecular abnormalities. Given its clinical and molecular heterogeneity, SRS could be considered as a spectrum.

Clinical Scoring of Disease Activity in Animal Models.

Disease severity in murine arthritis models, such as collagen-induced arthritis (CIA), is commonly assessed by clinical scoring of paw swelling and histological examination of joints. Clinical scoring using a qualitative scoring system of paw inflammation (paw thickness, width, or volume) over time is the standard method used for subjective quantification of arthritis activity. To evaluate paw swelling status, a quantitative method using three-dimensional T2-weighted flash sequence magnetic resonance imaging (MRI) is introduced. The efficacy of a therapeutic approach can be semiologically quantified using a clinical scoring system and an index of paw inflammation in CIA mice.

Multi-omics reveals that alkaline mineral water improves the respiratory health and growth performance of transported calves.

BACKGROUND: Long-distance transportation, a frequent practice in the cattle industry, stresses calves and results in morbidity, mortality, and growth suppression, leading to welfare concerns and economic losses. Alkaline mineral water (AMW) is an electrolyte additive containing multiple mineral elements and shows stress-mitigating effects on humans and bovines. RESULTS: Here, we monitored the respiratory health status and growth performance of 60 Simmental calves subjected to 30 hours of road transportation using a clinical scoring system. Within the three days of commingling before the transportation and 30 days after the transportation, calves in the AMW group (n = 30) were supplied with AMW, while calves in the Control group (n = 29) were not. On three specific days, namely the day before transportation (day -3), the 30th day (day 30), and the 60th day (day 60) after transportation, sets of venous blood, serum, and nasopharyngeal swab samples were collected from 20 calves (10 from each group) for routine blood testing, whole blood transcriptomic sequencing, serology detection, serum untargeted metabolic sequencing, and 16S rRNA gene sequencing. The field data showed that calves in the AMW group displayed lower rectal temperatures (38.967 ℃ vs. 39.022 ℃; p = 0.004), respiratory scores (0.079 vs. 0.144; p < 0.001), appetite scores (0.024 vs. 0.055; p < 0.001), ocular and ear scores (0.185 vs. 0.338; p < 0.001), nasal discharge scores (0.143 vs. 0.241; p < 0.001), and higher body weight gains (30.870 kg vs. 7.552 kg; p < 0.001). The outcomes of laboratory and high throughput sequencing data revealed that the calves in the AMW group demonstrated higher cellular and humoral immunities, antioxidant capacities, lower inflammatory levels, and intestinal absorption and lipogenesis on days -3 and 60. The nasopharynx 16S rRNA gene microbiome analysis revealed the different composition and structure of the nasopharyngeal microflora in the two groups of calves on day 30. Joint analysis of multi-omics revealed that on days -3 and 30, bile secretion was a shared pathway enriched by differentially expressed genes and metabolites, and there were strong correlations between the differentially expressed metabolites and the main genera in the nasopharynx. CONCLUSIONS: These results suggest that AMW supplementation enhances peripheral immunity, nutrition absorption, and metabolic processes, subsequently affecting the nasopharyngeal microbiota and improving the respiratory health and growth performance of transported calves. This investigation provided a practical approach to mitigate transportation stress and explored its underlying mechanisms, which are beneficial for the development of the livestock industry. Video Abstract.

Prevalence of respiratory disease in Irish preweaned dairy calves using hierarchical Bayesian latent class analysis.

Introduction: Bovine respiratory disease (BRD) has a significant impact on the health and welfare of dairy calves. It can result in increased antimicrobial usage, decreased growth rate and reduced future productivity. There is no gold standard antemortem diagnostic test for BRD in calves and no estimates of the prevalence of respiratory disease in seasonal calving dairy herds. Methods: To estimate BRD prevalence in seasonal calving dairy herds in Ireland, 40 dairy farms were recruited and each farm was visited once during one of two calving seasons (spring 2020 & spring 2021). At that visit the prevalence of BRD in 20 calves between 4 and 6 weeks of age was determined using thoracic ultrasound score (≥3) and the Wisconsin respiratory scoring system (≥5). Hierarchical Bayesian latent class analysis was used to estimate the calf-level true prevalence of BRD, and the within-herd prevalence distribution, accounting for the imperfect nature of both diagnostic tests. Results: In total, 787 calves were examined, of which 58 (7.4%) had BRD as defined by a Wisconsin respiratory score ≥5 only, 37 (4.7%) had BRD as defined by a thoracic ultrasound score of ≥3 only and 14 (1.8%) calves had BRD based on both thoracic ultrasound and clinical scoring. The primary model assumed both tests were independent and used informed priors for test characteristics. Using this model the true prevalence of BRD was estimated as 4%, 95% Bayesian credible interval (BCI) (1%, 8%). This prevalence estimate is lower or similar to those found in other dairy production systems. Median within herd prevalence varied from 0 to 22%. The prevalence estimate was not sensitive to whether the model was constructed with the tests considered conditionally dependent or independent. When the case definition for thoracic ultrasound was changed to a score ≥2, the prevalence estimate increased to 15% (95% BCI: 6%, 27%). Discussion: The prevalence of calf respiratory disease, however defined, was low, but highly variable, in these seasonal calving dairy herds.

Surgical Candidacy for Management of Laryngomalacia: A Proposed Scoring System.

Introduction: Identifying surgical candidacy for the management of laryngomalacia is a challenge. Objective: To develop a simple scoring system for surgical candidacy in laryngomalacia. Methods: Eighteen years retrospective observational study of children with laryngomalacia (LM) clinically categorized into mild, moderate and severe LM and were analyzed for surgical candidacy. Results: There were 113 children (age ranging from 5 days to 14 months), 44% being mild, 30% moderate and 26% severe LM. None in mild, 32% in moderate, and all in severe LM had surgical intervention. Presence of stridor on feeding or crying and isolated type 1 or type 2 LM on laryngoscopy were significant indicators for conservative treatment (p-< 0.0001). Moderate failure to thrive, retraction at rest/sleep, with low oxygen saturation while feeding/at rest were significantly higher in both moderate and severe groups with laryngoscopic evidence of combined type 1 and 2 in moderate LM (p < 00,001). Aspiration pneumonia, hospitalization, pectus and mean pulmonary arterial pressure of more than 25 mmHg with laryngoscopic findings of all three combined types were significantly higher in severe LM (p < 0.0001).A simple scoring system was then developed and it revealed that a score of 10 or more required surgical intervention. Conclusion and clinical significance: A clinical scoring system is being reported for the first time in medical literature to identify 'the difficult to treat' subset within moderate laryngomalacia category simplifying decision making in its management for otolaryngologists and pediatricians as well as a referral criterion for pediatric otolaryngologists' services.

A Case Report of Culture-Negative Necrotizing Fasciitis With Low Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score: A Diagnostic Dilemma.

The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is a diagnostic tool used to help clinicians identify necrotizing fasciitis (NF) in its early stages. This tool uses six laboratory values including the patient's white blood cell count, C-reactive protein level, serum sodium level, creatinine level, and hemoglobin level to help with risk stratification. Each of these laboratory values is assigned a point value and the total score is used to determine the likelihood that a patient has NF, with a score of 6 or higher considered to be strongly indicative. The LRINEC score has gained popularity in recent years, having been included in guidelines and society recommendations for the management of NF. However, some studies have challenged the validity of the LRINEC score. Prompt and accurate diagnosis of NF is imperative given the associated mortality rate, which can be as high as 30%-40%, especially if the diagnosis is delayed. We present a case of a patient with a delayed diagnosis of NF that was initially missed in the early stages in the setting of a low LRINEC, however, growing clinical suspicion eventually led to an accurate diagnosis and management.

Medical imaging for pancreatic diseases: Prediction of severe acute pancreatitis complicated with acute respiratory distress syndrome.

In this editorial we comment on the article published in the recent issue of the World Journal of Gastroenterology [2022; 28 (19): 2123-2136]. We pay attention to how to construct a simpler and more reliable new clinical predictive model to early identify patients at high risk of acute respiratory distress syndrome (ARDS) associated with severe acute pancreatitis (SAP), and to early predict the severity of organ failure from chest computed tomography (CT) findings in SAP patients. As we all know, SAP has a sudden onset, is a rapidly changing condition, and can be complicated with ARDS and even multiple organ dysfunction syndrome, and its mortality rate has remained high. At present, there are many clinical scoring systems for AP, including the bedside index for severity in AP, acute physiology and chronic health evaluation II, systemic inflammatory response syndrome, Japanese severe score, quick sepsis-related organ failure assessment, etc. However, some of these scoring systems are complex and require multiple and difficult clinical parameters for risk stratification. Although the aforementioned biomarkers are readily available, their ability to predict ARDS varies. Accor-dingly, it is extremely necessary to establish a simple and valuable novel model to predict the development of ARDS in AP. In addition, the extra-pancreatic manifestations of AP patients often involve the chest, among which pleural effusion and pulmonary consolidation are the more common complications. Therefore, by measuring the semi-quantitative indexes of chest CT in AP patients, such as the amount of pleural effusion and the number of lobes involved as pulmonary consolidation, it has important reference value for the early diagnosis of SAP complicated with ARDS and is expected to provide a basis for the early treatment of ARDS.

Impaired Vascular Endothelial Function is Associated with Peripheral Neuropathy in Patients with Type 2 Diabetes.

Purpose: It is believed that vascular endothelial dysfunction is involved in the occurrence of cardiovascular disease (CVD), and diabetic peripheral neuropathy (DPN) is associated with flow-mediated dilation (FMD), however, the correlation is still unclear. Aims of the present study is to explore the relationship between DPN parameters and FMD, providing a new approach for the prevention of CVD. Patients and Methods: A total of 272 patients with T2DM from the Department of Endocrinology of The First Hospital of Lanzhou University according to the grading criteria were selected. FMD was measured by a new vascular ultrasound system and patients were divided into FMD>7%, 4%≤FMD≤7%, and FMD<4% groups. The Toronto Clinical Scoring System (TCSS) was used to assess the severity of DPN. The nerve conduction studies (NCS) assessed large fibre neuropathy by nerve conduction velocity (CV), compound muscle action potential (CMAP) amplitude (Amp), and distal motor latency (DML). SPSS 25.0 was used for statistical analysis. Results: TCSS evaluation revealed that the percentage of patients with severe nerve injury was significantly higher in FMD<4% (70%) compared to FMD>7% (2%). Among the TCSS indicators of all subjects, the proportion of temperature disturbance was the most (73%), and joint position disturbance was the least (0). TCSS scores were negatively correlated with FMD (r=-0.756, p<0.001). More interesting, in FMD<4% group, CV and Amp were positively correlated with FMD, while DML was negatively correlated (p<0.05). Linear regression analysis model showed that different systolic blood pressure (SBP), triglyceride (TG), TCSS and CV had statistically different effects on FMD. Conclusion: High TCSS score and decreased CV of common peroneal and tibial nerves are risk factors of FMD injury, which provide potential value for timely prevention and treatment of cardiovascular diseases.

Comparing Clinical and Genetic Characteristics of De Novo and Inherited COL1A1/COL1A2 Variants in a Large Chinese Cohort of Osteogenesis Imperfecta.

Purpose: Nearly 85%-90% of osteogenesis imperfecta (OI) cases are caused by autosome dominant mutations of COL1A1 and COL1A2 genes, of which de novo mutations cover a large proportion, whereas their characteristics remain to be elucidated. This study aims to compare the differences in clinical and genetic characteristics of de novo and inherited COL1A1/COL1A2 mutations of OI, assess the average paternal and maternal age at conception in de novo mutations, and research the rate of nonpenetrance in inherited mutations. Materials and Methods: A retrospective comparison between de novo and inherited mutations was performed among 135 OI probands with COL1A1/COL1A2 mutations. Mutational analyses of all probands and their family members were completed by Sanger sequencing. A new clinical scoring system was developed to assess the clinical severity of OI quantitatively. Results: A total of 51 probands (37.78%) with de novo mutations and 84 probands (62.22%) with inherited mutations were grouped by the results of the parental gene verification. The proportion of clinical type III (P<0.001) and clinical scores (P<0.001) were significantly higher in de novo mutations. Missense mutations covered a slightly higher proportion of de novo COL1A1 mutations (46.34%) compared with inherited COL1A1 mutations (33.33%), however, lacking a significant difference (P=0.1923). The mean BMD Z/T-score at the lumbar spine in de novo mutations was -2.3 ± 1.5, lower than inherited mutations (-1.7 ± 1.8), but lacking statistical significance (P=0.0742). There was no significant difference between the two groups in OI-related phenotypes (like fracture frequency, blue sclera, and hearing loss) and biochemical indexes. In de novo mutations, the average paternal and maternal age at conception was 29.2 (P<0.05) and 26.8 (P<0.0001), respectively, which were significantly younger than the average gestational age of the population. Additionally, 98.04% of pedigrees (50/51) with de novo mutations were spontaneous conception. The rate of nonpenetrance of parents with pathogenic variants in the inherited mutation group was 25.64% (20/78). Conclusions: Our data revealed that the proportion of clinical type III and clinical scores were significantly higher in de novo mutations than in inherited mutations, demonstrating that de novo mutations are more damaging because they have not undergone purifying selection.

SIMPLE: A Novel Scoring System for Predicting Hemodynamically Significant Patent Ductus Arteriosus Without Echocardiographic Evaluation in Extremely Low Birth Weight Infants.

Aim: To develop a novel clinical scoring system for predicting hemodynamically significant patent ductus arteriosus (hsPDA) in extremely low birth weight (ELBW) infants. Methods: A prospective observational study was conducted among ELBW infants born in the study center during a 6-month period. Fourteen items were selected on a literature review basis and weighed by severity on an arbitrary 1-4 scale, the sum of which represented the Scoring preterm Infants for PDA cLinically without Echocardiographic evaluation (SIMPLE) score. The SIMPLE scores were compared at several time points during the first 3 days of life between two groups of patients: those with an hsPDA at echocardiography and those without. Results: A total of 48 ELBW infants were enrolled, of which 30 infants developed hsPDA. The SIMPLE scores of the infants with hsPDA were significantly greater than those of the infants who did not develop hsPDA. Cut-off SIMPLE scores that were significantly associated with detection of symptomatic hsPDA at each evaluation time point were identified. Conclusions: SIMPLE is the first scoring system that depends on the risk factors and clinical findings of ELBW infants for early prediction of hsPDA. It is simple, objective and easy to perform, and it does not require any additional tests and/or echocardiographic evaluation. We suggest that SIMPLE can be used as a screening tool for determining the need for echocardiographic evaluation in ELBW infants in order to minimize the number of unnecessary pediatric cardiology consultations.

Effect of Severity of Liver Cirrhosis on Surgical Outcomes of Hepatocellular Carcinoma After Liver Resection and Microwave Coagulation.

BACKGROUND: Liver resection (LR) and percutaneous microwave coagulation therapy (PMCT) are both considered as radical treatments for small hepatocellular carcinoma (HCC). However, it is still unclear whether to select LR or PMCT in HCC patients with different degrees of liver cirrhosis. The purpose of this study was to compare the efficacy of LR and PMCT in the treatment of solitary and small HCC accompanied with different degrees of liver cirrhosis. METHODS: In this study, 230 patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 108 received PMCT. The short- and long-term outcomes were compared between these two procedures. Severity of liver cirrhosis was evaluated by using clinical scoring system (CSS) as previously published. Subgroup analysis based on CSS was performed to evaluate the effect of severity of liver cirrhosis on surgical outcomes after LR and PMCT. RESULTS: There was no mortality within 90 days in both groups. Major complications were significantly more frequent in the LR group than in the PMCT group (18.8% vs. 4.6%, p<0.001). However, LR provided better surgical outcomes than PMCT. The 5-year overall survival (OS) rates for the LR and PMCT groups were 65.2% and 42%, respectively (p=0.006), and the corresponding disease-free survival (DFS) rates were 51.7% and 31.5%, respectively (p=0.004). Nevertheless, subgroup analysis showed that PMCT provided long-term outcomes that were similar to LR and lower surgical complications in HCC patients with CSS score≥4. CONCLUSIONS: LR may provide better OS and DFS rates than PMCT for patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function irrespective of liver cirrhosis. PMCT should be viewed as the optimal treatment for solitary and small HCC with severe cirrhosis.