Severe Grade Research Articles

Validation of a hand-held ultrasound device in the evaluation of aortic stenosis

Abstract Introduction Hand-held Ultrasound devices (HHUD) are increasingly used in routine clinical practice, although until recently they did not have continuous Doppler. There is no evidence on the usefulness of an HHUD for the assessment of aortic stenosis (AS) in real life. Objective To validate the use of a new HHUD device in a real-life scenario. Material and methods Observational, single-center and prospective study, including patients diagnosed with AS with a previous standard echocardiography. Patients were randomly recruited from a tertiary cardiac imaging laboratory. Immediately after the reference echocardiography performed by an imaging expert, a Cardiology trainee with ASE level II repeated the study blindly with an HHUD. Agreement between the two tests was evaluated by measuring the mean aortic valve gradient (mAG). An intraclass correlation coefficient (ICC) test, linear regression, and Bland-Altman test were performed to compare the two methods. Results 101 patients were recruited. The reference test calculated a mAG of 29 mmHg (19.8 - 42.2) versus a mAG of 27.2 mmHg (16.2 - 43.9) in HHUD. The statistical analysis showed a good correlation between both tests (ICC: 0.87 (95% CI: 0.79 -0.94) and r=0.89 (95% CI: 0.85-0.94) (Figure). The Bland-Altman test showed a non-significant underestimation (1.61 ± 0.9 mmHg; p= 0.09). The HHUD classified 29 cases as severe or major AS compared to 31 in the reference test (kappa= 0.81; 95% CI: 0.68 - 0.94). The HHUD showed an excellent agreement for classification of AS in at least severe AS grade. The kappa analysis had a value of 0.81 (95% CI 0.68 – 0.94) with a global agreement of 92.1%. The positive predictive value was 89.6%. The negative predictive value was 93.1%. Sensitivity and specificity were 83.8% and 95.7%. The rest of the variables evaluated showed poorer agreement. In those patients with obesity, worse acoustic window, atrial fibrillation and critical AS, the agreement was worse. Conclusions The new HHUD evaluated by an operator with limited experience showed good agreement with the reference echocardiographic device in determining the mean aortic gradient.Central picture

Intra, short and long-term results of mitral VIV for the degenerated surgical mitral prosthesis from italian VIV registry (MIVIV registry)

Abstract Background/Introduction Reoperation of failed bioprosthetic mitral valves is associated with significant morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) replacement was explored early in the development of THVs with transseptal/transfemoral (TS/TF) and transapical (TA) approaches. Purpose This is the first Italian Registry on mitral VIV and it was designed to explore contemporary MViV outcomes with all types of balloon expandable valves. The present study out of the registry aims to asses the >10 years follow-up outcomes in terms of mortality, gender diversity, and perioperative result. Methods Participating centers used standardized definitions to collect clinical information, including patient demographic characteristics, comorbidities, functional status, quality of life indexes, procedural details, and patient outcomes from consecutive MViV cases. Cohort of 265 patients was available for the primary analysis and follow-up too.The patients were grouped by 11 hospitals in Italy performing VIV for degenerated biological mitral prostheses. Results A total of 265 pts underwent mitral VIV due to bioprosthesis degeneration between January 2010 and January 2023. They have been subdivided by transfemoral (TF) with 117 (44%) pts and transapical (TA) with 148 (55,8%) pts. Most of the patients were of female sex (59,2%) and EuroScore II for surgical re-operation was 16.1%. Mixed disease (48%) was more common than mitral regurgitation (29%) and stenosis (22%). 69,8% of the total cohort was in class NYHA III and the mean LVEF was 54%.Otherwise, there were no significant demographic differences between patients undergoing TS and TA. In TF there was more severe PVL (5%)(p-value: 0,001) and much more cases of severe grade of stenosis (54,7%) and regurgitation (57%)(p-value< 0,0001). Considering intraoperative outcomes, technical success has been established in around 97,7% of the total cohort without difference btw groups. Only 3,3% died during hospitalization without difference between groups (P-value=0,735). LVOT obstruction has been seen in 3,4% in the case of TA and 0 for TF. Only 1,5% of the total cohort underwent surgical conversion as well as embolization in only 1,1%. Overall survival from the total cohort was 91,3% at >10 years, Figure 1. Concerning the freedom from cardiac death (CV death) was 96,6% in the total cohort at 13 years. Concerning the difference between access, the general survival is established at 97,4% in TF while 86,3% in TA (p-value =0,050)(Figure 2). Freedom from CV death was 99,1% in TF and 94,5 in TA (p-value=0,209). In gender analysis differentiation, the general survival in females was 98,5% in TF and 85,6% in TA at 13 years (p-value=0,056). Conclusion(s) Transcatheter MViV using a balloon-expandable valve is associated with high technical success, a low complication rate, and a solid long-term benefit in terms of survival. Transseptal access was associated with lower mortality compared with TA access.Figure 1Figure 2

Different right ventricular mechanics in atrial and ventricular secondary tricuspid regurgitation and their prognostic role. A multicentric three-dimensional echocardiography study

Abstract Background/Introduction Secondary tricuspid regurgitation (STR) can develop from markedly different etiologies. Both progressive dilation and dysfunction of the right atrium (atrial phenotype, ASTR), and adverse right ventricular (RV) remodeling (ventricular phenotype, VSTR) may result in STR. RV function is a major determinant of outcome in patients with STR. However, data about how RV function adapts to ASTR and VSTR are scarce, and the prognostic implications of RV mechanics in ASTR and VSTR remain to be clarified. Purpose Accordingly, we aimed to investigate the RV mechanical patterns in ASTR and VSTR and to examine their prognostic role using three-dimensional (3D) echocardiography. Methods We enrolled 192 patients with STR (60% women) who underwent clinically indicated transthoracic echocardiography in a multicentric prospective observational study. The primary outcome was defined as a composite of heart failure hospitalization or cardiac death. STR etiology was assessed based on the TVARC criteria (ventricular STR n=134, atrial STR n=58). STR severity was categorized using STR effective regurgitant orifice area according to current guidelines. We assessed RV function by measuring the tricuspid annular plane systolic excursion (TAPSE) by M-mode echocardiography and RV ejection fraction (EF) by 3D echocardiography. In addition, we imported the 3D RV meshes into the ReVISION software package (Argus Cognitive, Inc, Lebanon, USA) to quantify the relative contribution of the longitudinal (LEFi), radial (REFi), and anteroposterior motion components (AEFi) to total RV EF. Results ASTR and VSTR patients had comparable TAPSE (17±5 mm vs. 18±5 mm, p=0.10), while RV EF was significantly higher in ASTR (54±7% vs. 47±10% p<0.001). Although LEFi (0.37±0.08 vs. 0.38±0.10, p=0.95) and AEFi (0.45±0.08 vs. 0.44±0.11, p=0.53) were comparable between ASTR and VSTR, REFi was significantly lower in VSTR (0.52±0.09 vs. 0.47±0.12, p<0.01). RF EF was comparable among STR severity grades (mild vs. moderate vs. severe: 50±11 vs. 49±9 vs. 50±10%, respectively, p=0.85). Conversely, LEFi was significantly higher in mild and moderate STR vs severe STR (0.39±0.08 vs. 0.39±0.09 vs. 0.35±0.10, respectively, p=0.04). Using multivariable Cox regression based on variables significant in the univariate analysis, REFi was a significant independent predictor of outcome in the entire cohort (hazard ratio: 0.978 [CI, 0.959-0.999], p= 0.037). Conclusions Using 3D echocardiographic assessment, ASTR and VSTR patients demonstrated significant differences in the RV mechanical pattern, with a lower contribution of the radial contraction in the case of ventricular STR etiology. While RV EF was comparable between STR severity grades, the relative importance of the longitudinal motion significantly differed. Notably, the relative contribution of radial motion to RV function demonstrated independent prognostic value in patients with STR.RV mechanics in STR severity stages

Relationship Between Gross Motor Function and Nutritional Status of Children with Cerebral Palsy-A cross-sectional study in a Tertiary Care Hospital of Bangladesh

Background: Cerebral Palsy (CP) is one of the most common causes of chronic disability in children. Childhood malnutrition is a major public health issue in low- and middle-income countries. The gross motor function of children with CP can easily be assessed by the tool Gross Motor Function Classification System- Expanded &Revised (GMFCS-E&R). This study aimed to determine the relationship between GMFCS and nutritional status in children with cerebral palsy. Method: This cross-sectional observational study was conducted in the Department of Pediatric Neurology, IPNA, BSMMU from October 2019 to August 2020. All the patients aged 2-12 years were diagnosed as CP by clinical criteria and classified by GMFCS. Nutritional status (weight for age, height for age, weight for height, BMI) is assessed and classified according to the World Health Organization growth charts. Then linear and multinomial logistic regression methods to determine the associations between GMFCS and nutritional status. The correlation between motor function and nutritional status was assessed. Results: Among the 50 children 68% were male and 32% were female. The mean age of the CP children was 4.90±3.05 years. Most patients (66.0%) came from poor families followed by 24% from the middle class. Functionally majority of patients were in GMFCS level IV (28.0% ) and level V (20.0%). Maximum patients in spastic quadriplegia 42%, spastic hemiplegia 16%. The level of GMFCS was associated with nutritional status, as determined by anthropometry. Moderate and severe underweight significantly related with GMFC level IV and V. Moderate and severe stunted was significantly related with IV and V GMFC level. Moderate wasted was significantly related to GMFC levels III and IV. Mild malnutrition was significantly with GMFC level II and III. Severe malnutrition is significantly related to GMFC level IV and V. Conclusion: This study showed majority of cerebral palsy cases had severe functional gross motor disability and also severe grade of malnutrition. A significant association between severe grade of malnutrition and severe grade of motor disability was found. J Bangladesh Coll Phys Surg 2024; 42: 342-349

Association of Dairy Foods in Acne Vulgaris

Background: Acne vulgaris is one of the most commonly found skin problems affecting teenagers and adolescents. Dietary foods particularly dairy products consist of milk or any of its food made from milk are frequently regarded by patients and clinicians as a cause or aggravator of acne. As there are very limited studies found on this regard, this study was aimed to find the association of dairy foods in acne vulgaris. Methods: This wasa cross-sectional analytical study and was carried out in the Dermatology and Venereology department of Shaheed Suhrawardy Medical College Hospital. Total 260 patients were selected by appropriate inclusion criteria equally into two groups: Group A (diagnosed with acne vulgaris, n=130) and group B (patients not having acne vulgaris, n=130). A thorough history of every patient and face to face interview was taken by a predesigned questionnaire after getting the written informed consent of the patient. Data were collected in predetermined data collection form. Result were subjected to standard statistical evaluation and were analyzed by SPSS-24. Results: According to the age group, majority of the acne patients were between 10-20 years (75.4% in group A and 63.8% in group B, p<0.05), though mean age in both groups were statistically similar (18.53±5.78 and 17.29±4.59 years, respectively). Also, female respondents were predominant in both groups (80.8% and 72.3%). The risk was increased in those with a family history of acne in siblings (OR2.449, p=0.021;95% CI,1.145-5.238) and the risk was reduced in subjects doing physical exercise. Papules (35.4%) and comedones (27.7%) were most common lesion and mostly found in forehead (74.6%) and left (68.5%) and right (63.1%) cheeks. According to global acne severity grading, majority had mild form of acne (83.1%) and use of cosmetics (43.8% vs. 30%), topical steroid (34.6% vs. 16.9%), taking fastfood (24.6% vs. 14.6%) and less water intake (36.9% vs. 18.5%) also significantly higher among acne patients. Multivariate regression analysis showed, dairy products such as whole milk (OR 1.984, p=0.022), chocolate (2.490, p=0.004), chips (OR 3.207, p<0.001), Pizza (OR 2.388, p=0.021) and red meat (OR 3.055, p=0.009) were significant risk for developing acne vulgaris. Also, whole milk (3.050, p=0.01), chocolate (3.817, p=0.004) and pizza (3.822, p=0.005) were independent risk factors for moderate to severe acne. Conclusion: This study found an association between high dairy product consumption and acne in adolescents, indicating that dairy consumption may be a contributing factor for developing acne vulgaris. J Shaheed Suhrawardy Med Coll 2022; 14(2): 25-33

Role of clipping in aneurysmal subarachnoid hemorrhage: a post hoc analysis of the Earlydrain trial

The choice between clipping and coiling of ruptured cerebral aneurysms in subarachnoid hemorrhage (SAH) remains controversial. The recently published Earlydrain trial provides the opportunity to analyze the latest clip-to-coil ratio in German-speaking countries and to evaluate vasospasm incidence and explorative outcome measures in both treatment modalities. We performed a post hoc analysis of the Earlydrain trial, a multicenter randomized controlled trial investigating the use of an additional lumbar drain in aneurysmal SAH. The decision whether to clip or to coil the ruptured aneurysm was left to the discretion of the participating centers, providing a real-world insight into current aneurysm treatment strategies. Earlydrain was performed in 19 centers in Germany, Switzerland, and Canada, recruiting 287 patients with aneurysmal SAH of all severity grades. Of these, 140 patients (49%) received clipping and 147 patients (51%) coiling. Age and clinical severity based on Hunt-Hess/WFNS grades and radiological criteria were similar. Clipping was more frequently used for anterior circulation aneurysms (55%), whereas posterior circulation aneurysms were mostly coiled (86%, p < 0.001). In high-volume recruiting centers, 56% of patients were treated with clipping, compared to 38% in other centers. A per-year analysis showed a stable and balanced clipping/coiling ratio over time. Regarding vasospasm, 60% of clipped versus 43% of coiled patients showed elevated transcranial Doppler criteria (p = 0.007), reflected in angiographic vasospasm rates (51% vs. 38%, p = 0.03). In contrast to the Earlydrain main results establishing the superiority of an additional lumbar drain, explorative outcomes after clipping and coiling measured by secondary infarctions, mortality, modified Rankin Score, Glasgow Outcome Scale Extended, or Barthel-Index showed no significant differences after discharge and at six months. In clinical practice, aneurysm clipping is still a frequently used method in aneurysmal SAH. Apart from a higher rate of vasospasm in the clipping group, an exploratory outcome analysis showed no difference between the two treatment methods. Further development of periprocedural treatment modalities for clipped ruptured aneurysms to reduce vasospasm is warranted.

Impact of Atezolizumab + Bevacizumab Therapy on Health-Related Quality of Life in Patients with Advanced Hepatocellular Carcinoma

Background/Objectives: Health-related quality of life (HRQoL) is critical in patients with hepatocellular carcinoma (HCC). It has become a key endpoint in the evaluation of new therapies, including atezolizumab + bevacizumab (Atezo + Bev) therapy. Methods: This study explored the factors associated with treatment efficacy, treatment duration, and overall survival (OS) in patients with advanced HCC undergoing Atezo + Bev therapy. We included 58 consecutive patients with HCC receiving Atezo + Bev from 19 November 2020, to 28 December 2023, who were followed up until the end of the study or death. We analyzed the relationships between baseline characteristics, adverse events (AEs), and HRQoL and efficacy, OS, and treatment duration. Results: The demographic (older men) and baseline characteristics (Child–Pugh score of 5, Barcelona Clinic Liver Cancer Stage C) were consistent with those of previous studies. The treatment demonstrated promising efficacy with a disease control rate of 71.2%, but HRQoL scores in five functional domains and seven symptoms worsened significantly within the first 3 months. Notably, better baseline cognitive and physical function scores and absence of severe (grade ≥ 2) hypoalbuminemia were associated with an improved objective response rate, longer treatment duration, and better OS. Conclusions: These findings underscore the importance of monitoring and managing treatment-related AEs and maintaining the HRQoL. They also highlight the crucial and reassuring role of multidisciplinary care in enhancing treatment outcomes in this cohort.

Predicting neonatal mortality prior to discharge from hospital in prenatally diagnosed left congenital diaphragmatic hernia.

To evaluate the association of standardized prenatal imaging parameters and immediate neonatal variables with mortality prior to discharge in infants with isolated left congenital diaphragmatic hernia (LCDH), and to compare the performance of ultrasound- and magnetic resonance imaging (MRI)-based severity grading for the prediction of neonatal mortality. This was a retrospective study of infants with prenatally diagnosed isolated LCDH referred to a single tertiary center between 2008 and 2020. Fetuses with right or bilateral congenital diaphragmatic hernia, additional major structural anomaly or known genetic condition, as well as cases that underwent fetal intervention or declined postnatal intervention, were excluded. Ultrasound and MRI images were reviewed retrospectively. Univariable and multivariable analyses were performed, incorporating prenatal and immediate neonatal factors to analyze the association with neonatal mortality prior to discharge, and a prediction calculator was generated. The performance of ultrasound and that of MRI for the prediction of neonatal mortality were compared. Of 253 pregnancies with fetal CDH, 104 met the inclusion criteria, of whom 77 (74%) neonates survived to discharge. Seventy-five fetuses underwent both prenatal ultrasound and MRI. On multivariable analysis, observed/expected (o/e) lung-to-head ratio and o/e total fetal lung volume were associated independently with neonatal death (adjusted odds ratio, 0.89 (95% CI, 0.83-0.95) and 0.90 (95% CI, 0.84-0.97), respectively), whereas liver position was not. There was no significant difference in predictive performance between using ultrasound and MRI together (area under the receiver-operating-characteristics curve (AUC), 0.85 (95% CI, 0.76-0.93)) compared with using ultrasound alone (AUC, 0.81 (95% CI, 0.72-0.90); P = 0.19). The addition of neonatal parameters (gestational age at birth and small-for-gestational age) did not improve model performance (AUC, 0.87 (95% CI, 0.80-0.95)) compared with the combined ultrasound and MRI model (P = 0.22). There was poor agreement between severity assessment on ultrasound and MRI (Cohen's κ, 0.19). Most discrepancies were seen among cases deemed to be non-severe on ultrasound and severe on MRI, and outcomes were more consistent with MRI-based prognostication. In fetuses with prenatally diagnosed isolated LCDH, mortality prediction using standardized ultrasound and MRI measurements performed reasonably well. In cases classified as non-severe on ultrasound, MRI is recommended, as it may provide more accurate prognostication and assist in the determination of candidacy for fetal intervention. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Precise grading of non-muscle invasive bladder cancer with multi-scale pyramidal CNN

The grading of non-muscle invasive bladder cancer (NMIBC) continues to face challenges due to subjective interpretations, which affect the assessment of its severity. To address this challenge, we are developing an innovative artificial intelligence (AI) system aimed at objectively grading NMIBC. This system uses a novel convolutional neural network (CNN) architecture called the multi-scale pyramidal pretrained CNN to analyze both local and global pathology markers extracted from digital pathology images. The proposed CNN structure takes as input three levels of patches, ranging from small patches (e.g., 128×128\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$128 \ imes 128$$\\end{document}) to the largest size patches (512×512\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$512 \ imes 512$$\\end{document}). These levels are then fused by random forest (RF) to estimate the severity grade of NMIBC. The optimal patch sizes and other model hyperparameters are determined using a grid search algorithm. For each patch size, the proposed system has been trained on 32K patches (comprising 16K low-grade and 16K high-grade samples) and subsequently tested on 8K patches (consisting of 4K low-grade and 4K high-grade samples), all annotated by two pathologists. Incorporating light and efficient processing, defining new benchmarks in the application of AI to histopathology, the ShuffleNet-based AI system achieved notable metrics on the testing data, including 94.25% ± 0.70% accuracy, 94.47% ± 0.93% sensitivity, 94.03% ± 0.95% specificity, and a 94.29% ± 0.70% F1-score. These results highlight its superior performance over traditional models like ResNet-18. The proposed system’s robustness in accurately grading pathology demonstrates its potential as an advanced AI tool for diagnosing human diseases in the domain of digital pathology.

Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis

Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.

Development and validation of a pediatric internationally agreed ultrasound knee synovitis protocol (PIUS-knee) by the PReS imaging working party

ObjectivesTo identify an optimal pediatric musculoskeletal ultrasound (MSUS) protocol for the detection of knee arthritis in patients with juvenile idiopathic arthritis (JIA) including a comparison with existing protocols. Secondary aims were to correlate MSUS-identified B-Mode (BM) and Power Doppler-Mode (PD) synovitis with clinical findings.MethodsConsecutive JIA patients with confirmed knee arthritis after clinical examination underwent a thorough MSUS study protocol which included views identified and consented by the Pediatric Rheumatology european Society (PReS) Imaging Working Party for the detection of synovitis. In total eight views including measurement of the suprapatellar recess were included. Scoring of synovitis followed the pediatric OMERACT criteria (BM and PD severity grading 0 to 3). Interobserver reliability of BM and PD was tested before study begin. Previously published MSUS protocols for knee synovitis were also identified from the literature and their scan protocols compared to identify differences in sensitivity for synovitis according to the number and specific type of views included. Finally, a clinically applicable MSUS protocol for knee synovitis could be proposed.ResultsIn 114 patients with clinically active knee inflammation, BM positivity (grading ≥ 1) was most frequently detected in the suprapatellar longitudinal and transverse scans performed in any positioning (frequency 97–99% in suprapatellar longitudinal in 30° or neutral respectively). PD positivity was however higher in these views performed in 30° flexion compared to neutral. Intrasynovial PD positivity (grading ≥ 1) was most frequently detected in the lateral parapatellar (69%, sensitivity 0.68, specificity 0.98), medial parapatellar (frequency 67%, sensitivity 0.67, specificity 1.0), the longitudinal lateral (68%, sensitivity 0.67, specificity 0.98) and suprapatellar transverse in 30° (frequency 64%, sensitivity 0.64, specificity 1.0). A combination of five views was the most sensitive for BM and PD synovitis. The suprapatellar recess size was analyzed by age and gender. For each group, the recess was wider in knees with arthritis than without (p < 0.001). Interobserver reliability of BM and PD positivity showed 85% agreement, with kappa 0.74 (very good). Three published studies with knee synovitis MSUS protocols were identified, which included a range of 1–3 views. Evaluation of the sensitivity of positive PD findings of each of these protocols reached a range of 53–83%; the highest sensitivity (91%) was achieved with the 5 views as identified by this study. These five views were therefore combined to form the Pediatric Internationally agreed Ultrasound (PIUS) knee protocol.ConclusionBM and PD positivity reliably correlated with the identification of pathological findings in knees of patients with JIA. From an internationally agreed protocol of eight images, a combination of five showed the greatest sensitivity for synovitis. This protocol, termed ‘PIUS-Knee’ performed well when compared to existing protocols.

Short-term neurologic outcomes in pediatric extracorporeal membrane oxygenation are proportional to bleeding severity graded by a novel bleeding scale.

This study aimed to characterize the severity of bleeding and its association with short-term neurologic outcomes in pediatric ECMO. Multicenter retrospective cohort study of pediatric ECMO patients at 10 centers utilizing the Pediatric ECMO Outcomes Registry (PEDECOR) database from December 2013-February 2019. Subjects excluded were post-cardiac surgery patients and those with neonatal pathologies. A novel ECMO bleeding scale was utilized to categorize daily bleeding events. Poor short-term neurologic outcome was defined as an unfavorable Pediatric Cerebral Performance Category (PCPC) or Pediatric Overall Performance Category (POPC) (score of >3) at hospital discharge. This study included 283 pediatric ECMO patients with a median (interquartile range [IQR]) age of 1.3years [0.1, 9.0], ECMO duration of 5days [3.0, 9.5], and 44.1% mortality. Unfavorable PCPC and POPC were observed in 48.4% and 51.3% of patients at discharge, respectively. Multivariable logistic regression analysis included patient's age, cannulation type, duration of ECMO, need for cardiopulmonary resuscitation, acute kidney injury, new infection, and vasoactive-inotropic score. As the severity of bleeding increased, there was a corresponding increase in the likelihood of poor neurologic recovery, shown by increasing odds of unfavorable neurologic outcome (PCPC), with an adjusted odds ratio (aOR) of 0.77 (confidence interval [CI] 0.36-1.62), 1.87 (0.54-6.45), 2.97 (1.32-6.69), and 5.56 (0.59-52.25) for increasing bleeding severity (grade 1 to 4 events, respectively). Similarly, unfavorable POPC aOR (CI) was 1.02 (0.48-2.17), 2.05 (0.63-6.70), 5.29 (2.12-13.23), and 5.11 (0.66-39.64) for bleeding grade 1 to 4 events. Short-term neurologic outcomes in pediatric ECMO are proportional to the severity of bleeding events. Strategies to mitigate bleeding events could improve neurologic recovery in pediatric ECMO.

A novel deep learning approach for automated grading of knee osteoarthritis severity

A novel deep learning approach for automated grading of knee osteoarthritis severity

Association of vertebral fractures with worsening degenerative changes of the spine: a longitudinal study.

Vertebral compression fractures (VFs) and spinal degeneration are both common causes of back pain, particularly in older adults. Previous cross-sectional studies have shown a potential association between these entities, but there is limited evidence on the role of VFs in spinal degeneration. In this longitudinal study, we evaluated the association between prevalent VFs and the subsequent progression of facet joint osteoarthritis (FJOA) and intervertebral disc height narrowing (DHN), using data from the Framingham Heart Study Offspring and Third Generation Multi-Detector Computed Tomography study. Summary indices representing the total burden of each spinal parameter (VFs, DHN and FJOA) were calculated for each individual. We hypothesized that prevalent VFs are associated with worsening spinal degeneration. 370 (31%) of 1197 participants, had a baseline (prevalent) VF. The change in summary index of DHN over the follow-up period was significantly higher in those with versus without prevalent VF (difference in change in DHN 0.38, 95% CI 0.18 to 0.59, P<.001), but the change in summary index of FJOA was similar between those with and without prevalent VF. However, once adjusted for age, sex, cohort, smoking status, body mass index, and baseline DHN, the change in summary index of DHN did not differ by prevalent VF status. There was a modestly higher change in the FJOA summary index in those with prevalent VFs compared to those without in the fully adjusted model (difference in change in FJOA 0.62, 95% CI -0.01 to 1.24, P=.054), driven primarily by those with severe (grade 3) VF (difference in change in FJOA 4.48, 95% CI 1.99 to 6.97). Moreover, there was greater change in the summary index of FJOA with increasing severity of prevalent VF (linear trend P=.005). Beyond the established morbidity and mortality associated with VFs, our study suggests that VFs may also lead to worsening spine osteoarthritis.

Construction of a comprehensive meteorological risk index for wheat Fusarium head blight prediction based on more than a half-century of monitoring data.

Fusarium head blight (FHB) represents a critical threat to wheat production globally, not only reducing yields but also contaminating crops with harmful mycotoxins. This study aimed to elucidate new spatiotemporal patterns of FHB incidence and to develop a comprehensive meteorological risk index to enhance scientific prevention and control of the disease. Through the analysis of annual and decadal variations from 1965 to 2023, the study assessed FHB trends across four agricultural regions (I, II, III, and IV) in Jiangsu Province, located in the middle and lower reaches of the Yangtze River-a hotspot for FHB in China. Key findings include: Since 1965, Regions I and III consistently exhibited higher FHB incidence rates compared to Regions II and IV. Post-2000, there was a notable increase in years with high incidence rates, with Region III overtaking Region I as the region with the highest incidence. Since 2010, occurrences of FHB reaching the most severe grade (Grade 5) have surpassed those in previous decades across all regions. The study also revealed a stronger correlation between meteorological factors (cumulative precipitation, number of days with rainfall ≥ 0.1 mm, total rainy days with ≥ 2 and ≥3 consecutive days of rain, total rainy days with both average daily air temperature ≥ 15 °C and daily rainfall ≥ 0.1 mm, days with average daily relative humidity ≥ 85%, cumulative sunshine hours, and cumulative cloudy days) and the FHB incidence rates during the heading-flowering-grain filling period in Regions I, II, and III, compared to the heading-flowering period alone. This indicates that optimal temperature and high humidity during the grain filling stage significantly contribute to the final FHB incidence rates. Despite the less apparent correlation between temperature changes and disease rates, the significant warming trend observed since 2000 has likely fostered conditions conducive to the proliferation of FHB. The comprehensive meteorological risk index, constructed to incorporate key meteorological factors during the heading-flowering-filling period, showed a strong correlation with actual disease incidences. The index demonstrated fitting accuracy rates of 84.7% for Region I, 72.9% for Region II, 83.1% for Region III, and 90.9% for Region IV, underscoring its effectiveness in predicting FHB occurrences. This tool offers both convenience and practicality, providing valuable insights for strategically managing FHB risks based on local weather conditions.

Screening and monitoring of diabetic retinopathy in community care: the effectiveness of single-field vs multi-field fundus photography.

This study aimed to evaluate the effectiveness of single-field fundus photography for diabetic retinopathy (DR) screening and monitoring versus six-field imaging in community settings. Adults aged ≥30 years with type 2 diabetes from 15 communities in Northeast China were recruited for this prospective cohort study (n=2006 at baseline and n=1456 at follow-up). Participants underwent both single-field and six-field digital fundus photography at baseline and follow-up visits (mean duration of 21.2±3.2 months). Photographs were graded using international standards. Agreement in DR severity grading, referral recommendations, and detection of DR progression were compared between single-field and six-field fundus photography. Single-field grading showed substantial agreement with multi-field grading in classifying DR severity (81.9% identical at baseline, 80.6% at follow-up, Gwet's AC1 0.79 and 0.77). For referring eyes with moderate non-proliferative DR or worse, single-field grading had ∼70% sensitivity and 100% specificity compared to six-field grading. Single-field grading identified 74.9% or 79.7% of eyes progressing or regressing by six-field grading, respectively. Single-field fundus photography demonstrated reasonable effectiveness for DR screening and monitoring in a community setting, supporting its use for improving access to DR detection. However, reduced sensitivity compared to multi-field imaging should be acknowledged.

Severe myelotoxicities related to Th1, Th2, Th17 and Treg CD4+ T cells subpopulations and their cytokine profiles in Mexican children with acute lymphoblastic leukemia during induction of chemotherapy

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer in the world, and the myelotoxicities due to chemotherapy can lead to severe infections and hemorrhages with high morbidity and mortality. The immune response has implications in the severity of cancer or survival. This immune response is associated with the predominant subpopulations CD4+ T cells and their effector cytokines. However, it is not known if the immune responses are associated with severe myelotoxicities and mortality in children with ALL. Methods To evaluate the contributions of immunological factors on ALL severe myelotoxicities, we identified the Th1, Th2, Th9, Th17, Th22 and Tregs subpopulations of CD4+ T cells according to their chemokine receptor expression patterns in peripheral blood mononuclear cells by flow cytometry. We evaluated also their cytokines levels by Milliplex in serum from 10 children with ALL at diagnosis (day 0), during induction (day 19) and at the end of induction (day 30) between April 2022 and July 2023. Clinical characteristics such age, sex, type and risk of ALL, hemoglobin and platelets levels, absolute neutrophil count, grade of severity and type of myelotoxicities, infections, and hemorrhages were collected. Clinical outcomes as hospitalization care requirements, ICU admission, leukemia remission or relapsed and mortality were followed and documented. Results The age of children was 8.9 years, (SD,5.6; range 2-16), 60% were male sex, all children had pre- B ALL diagnosis, and 80% were intermediate risk-ALL. Th1 cells were predominant at diagnosis (8.1%) and at the end of induction (7.8%), and Th2 cells at day 19 (7.4%), whereas Th17 were significantly decreased at day 30 (2.6%) (p&amp;lt;0.05). Four patients presented bloodstream infection, two by Gram-positive bacteria (Micrococcus, and Streptococcus), one by Klebsiella pneumoniae antimicrobial resistant, and one by Trichosporum asahii. Severe myelotoxicities were presented in 20% of the patients at day19, and in 30% at day 30. Remission was documented in all patients at day 30 and one was identified with early relapse in the follow-up. Three patients (30%) presented poor outcomes, requiring care in ICU and one died (10%) due to fungal infection. Treg cells were significantly predominant in the children who died by fungal infection (p&amp;lt;0.05), with IL-10 level of 84.6 pg/mL but not detectable IL-35 levels. Conclusion Th17 and Treg subpopulations of CD4+ T cells can play an essential role in immune microenvironment during induction related with the severity of the myelotoxicities and infections, and cytokine IL-10 could be used as marker of infection outcome.

LABORATORY PREDICTORS FOR DIAGNOSING COLORECTAL ANASTOMOTIC LEAKAGE.

An important concern in oncological coloproctology is colorectal anastomotic leakage (AL), which occurs in 3.5%-21% of patients. Predicting the occurrence of failure based on the results of laboratory markers can be decisive for the treatment of this complication. To improve the early diagnosis of AL by establishing combinations and threshold values of laboratory markers - predictors of the inflammatory process. The prospective study, conducted from 2020 to 2023, included 213 rectal cancer patients who underwent low anterior resection after neoadjuvant chemoradiotherapy. The inflammatory biomarkers were assessed before surgery and on the 3rd, 5th, and 7th days of the postoperative period. AL diagnosed in 25 (11.74%) patients by the grade of severity was as follows: A (radiological) in 7 (3.29%) patients; B (clinical) - 4 (1.88%); C (clinically expressed, peritonitis) - 11 (5.16%), and P (late) - 3 (1.41%) patients. The changes in the laboratory indicators of the inflammatory response such as С-reactive protein (CRP), procalcitonin (PCT), the counts of neutrophils (NEU), lymphocytes (LYM), platelets (PLT), and neutrophil/lymphocyte ratio (NLR) were significant only in B or C AL grades. Among them, only three indicators were identified as significant for predicting AL when assessed 24 h before the onset of this complication, namely LYM (threshold value ≤ 0.97 × 103/mm3, sensitivity 66.7% and specificity 81.3%, p < 0.001); PLT (threshold value > > 257 103/mm3, sensitivity 58.6%, and specificity 86.7%, p < 0.001); and NLR (threshold value > 4.42, sensitivity 58.1%, and specificity 86.7%, p < 0.001). The three-factor model based on these selected indicators was set up, and the prognosis index (Prog) was proposed with the decision threshold Progcrit = 2.23. The sensitivity of the model was 80% (95% CI 51.9%-95.7%), and the specificity - 74.2% (67.6%-80.2%). Based on the routine laboratory predictors used in the complex diagnosis of AL, B or C AL grades may be predicted allowing for the timely effective early diagnosis, medication, and surgical intervention..

A phase 2 multicenter trial of ruxolitinib to treat bronchiolitis obliterans syndrome after allogeneic HCT

AbstractBronchiolitis obliterans syndrome (BOS) occurring after allogeneic hematopoietic cell transplantation (HCT) is a high-risk manifestation of chronic graft-versus-host disease. In this prospective, multicenter phase 2 trial, adult participants with BOS were treated with ruxolitinib 10 mg twice daily, continuously in 28-day cycles for up to 12 cycles. Participants enrolled into newly diagnosed (<6 months since BOS diagnosis, cohort A) or established (≥6 months since BOS diagnosis, cohort B) disease cohorts. The primary objective was to evaluate the early treatment effect of ruxolitinib, assessed by the change in forced expiratory volume in 1 second (FEV1) at 3 months compared with enrollment. The primary end point differed according to cohort (cohort A, improvement, defined as ≥10% increase in FEV1; cohort B, stabilization, defined as an absence of ≥10% decrease in FEV1). Between 2019 and 2022, 49 participants meeting the criteria for BOS were enrolled and treated (cohort A, n = 36; cohort B, n = 13). The primary end point was achieved by 27.8% of participants with new BOS and 92.3% of participants with established BOS. According to the 2014 National Institutes of Health Consensus Criteria, the best lung-specific overall response rate on ruxoltinib for the 49 participants was 34.7% (16.3% complete response and 18.4% partial response), with most responses occurring in mild or moderate disease. Noninfectious severe (grade ≥3) treatment-emergent adverse events were infrequent. Nine severe infectious events occurred and were largely respiratory in nature. These results support the use of ruxolitinib in the management of BOS after allogeneic HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03674047.

Automatic Acne Severity Grading with a Small and Imbalanced Data Set of Low-Resolution Images.

Developing automatic acne vulgaris grading systems based on machine learning is an expensive endeavor in terms of data acquisition. A machine learning practitioner will need to gather high-resolution pictures from a considerable number of different patients, with a well-balanced distribution between acne severity grades and potentially very tedious labeling. We developed a deep learning model to grade acne severity with respect to the Investigator's Global Assessment (IGA) scale that can be trained on low-resolution images, with pictures from a small number of different patients, a strongly imbalanced severity grade distribution and minimal labeling. A total of 1374 triplets of images (frontal and lateral views) from 391 different patients suffering from acne labeled with the IGA severity grade by an expert dermatologist were used to train and validate a deep learning model that predicts the IGA severity grade. On the test set we obtained 66.67% accuracy with an equivalent performance for all grades despite the highly imbalanced severity grade distribution of our database. Importantly, we obtained performance on par with more tedious methods in terms of data acquisition which have the same simple labeling as ours but require either a more balanced severity grade distribution or large numbers of high-resolution images. Our deep learning model demonstrated promising accuracy despite the limited data set on which it was trained, indicating its potential for further development both as an assistance tool for medical practitioners and as a way to provide patients with an immediately available and standardized acne grading tool. chinadrugtrials.org.cn identifier CTR20211314.