Unfavorable Long-term Outcomes Research Articles

Factors of early neonatal maladaptation of late preterm infants

Late preterm infants are more susceptible to various unfavorable factors than preterm infants. The leading place in the structure of morbidity, as well as the formation of long-term unfavorable outcomes in this group of children is occupied by respiratory disorders, impaired or delayed neurodevelopment. In order to study in detail the pathological conditions leading to adaptation disorders, we retrospectively analyzed the data of developmental histories of late premature infants and delivery histories. The relationship between placental abnormalities, including fetal growth and developmental delays, fetal conception, history of pregnancy termination, low birth weight, age of the woman in labor and increased need for respiratory support, as well as clinical manifestations of cerebral ischemia in newborns at 34 0/7–36 6/7 weeks gestation was revealed

The BEnefit of LONGitudinal Micro-Incisions Prior to Paclitaxel-Coated Balloon Angioplasty (BELONG Study) in Patients With Lower Extremity Arterial Disease: Clinical Outcomes at 12 Months.

Angioplasty of lower extremity arteries with calcification may result in flow-limiting dissection requiring bail-out stenting with unfavorable long-term outcomes. Vessel preparation prior to angioplasty may improve immediate results of the angioplasty and long-term patency. This prospective study assessed the 12-month outcomes of patients who underwent novel vessel preparation catheter, the FLEX Vessel Prep™ System (FLEX VP), prior to drug-coated balloon angioplasty (DCB-PTA). This investigator-initiated single-arm prospective trial enrolled patients with symptomatic lower extremity peripheral artery disease with de novo, restenotic, or in-stent stenosis of the superficial femoral or popliteal arteries. Target lesions were prepared using FLEX VP that created 12 longitudinal micro-incisions before drug-coated balloon angioplasty. Forty-three lesions in 41 patients were treated in this study with an average lesion length of 118 mm (10-291 mm), average stenosis of 82% (40-100%), and an occlusion rate of 27.9% with an average occlusion length of 89 mm (10-272 mm). Calcification was observed in 85.7% of the lesions, with 66.7% of lesions demonstrating grade 3 or 4 of the Peripheral Arterial Calcification Scoring System. After FLEX VP and DCB-PTA, 92.7% of patients were absent of flow-limiting dissections. Stenting occurred in 39% (16/41) patients (median stent length 40 mm) for residual stenosis (15 patients) and flow-limiting dissection (1 patient). There was one death prior to the 12-month follow-up, not related to the index procedure. Freedom from clinically driven target lesion revascularization at 12 months was 97.5% (39/40). Rutherford classification shifted from 41.5% Class ≥3 at baseline to 95% Class ≤1 at 12 months. There were no amputations at 12 months. Vessel preparation with longitudinal micro-incisions of complex and calcified lesions prior to angioplasty was associated with few flow-limiting dissections. The majority of stents were placed to treat focal residual stenosis, using the shortest available stent length at the time of the study (40 mm) for the majority. Only one stent was needed to treat a flow-limiting dissection. The 97.5% freedom from clinically driven target lesion revascularization (CDTLR) and symptom relief at 12 months suggest that vessel preparation via FLEX VP provides value in maintaining long-term outcomes in patients with highly calcified superficial femoral artery (SFA) or popliteal lesions. Vessel preparation with longitudinal micro-incisions is a short and efficient intervention associated with promising clinical outcomes and patency rate 12 months after treatment of long and calcified occlusions or stenosis of the femoral and popliteal arteries. This innovative vessel preparation provides post-procedure less residual stenosis and more favorable dissection morphology, decreasing the placement of stent and especially their length. Vessel preparation by longitudinal incisions also favors optimal distribution of anti-restenotic drug in the lesion and thus prevents further intervention due to restenosis.

Long-term Follow-up Optical Coherence Tomography Assessment of Primary Percutaneous Coronary Intervention for Unprotected Left Main

Background: Elective unprotected left main (ULM) percutaneous coronary intervention (PCI) has long-term mortality rates comparable to surgical revascularization, thanks to advances in drug-eluting stent (DES) design, improved PCI techniques, and frequent use of intravascular imaging. However, urgent PCI of ULM culprit lesions remains associated with high in-hospital mortality and unfavourable long-term outcomes, including DES restenosis and stent thrombosis (ST). This analysis aimed to examine the long-term outcomes and healing of DES implanted in ULM during primary PCI using high-resolution optical coherence tomography (OCT) imaging. Methods: A total of 15 consecutive patients undergoing long-term OCT follow-up of ULM primary PCI from a high-volume center were included in this analysis. During the index primary PCI all subjects underwent angio-guided DES implantation, and follow-up was uneventful in all but one subject who had a non-target PCI lesion. The primary endpoint was the percentage of covered, uncovered, and malappossed stent struts at long-term follow-up. Secondary endpoints included quantitative and qualitative OCT measurements. For the left main bifurcation, a separate analysis was performed for three different segments: left main (LM), polygon of confluence (POC) and distal main branch (dMB), in all cases. Results: The average follow-up interval until OCT was 1580 ± 1260 days. Despite aorto-ostial stent protrusions in 40% of patients, optimal image quality was achieved in 93.3% of cases. There were higher rates of malapposed (11.4 ± 16.6 vs. 13.1 ± 8.3 vs. 0.3 ± 0.5%; p < 0.001) and lower rates of covered struts (81.7 ± 16.8 vs. 83.7 ± 9.2 vs. 92.4 ± 6.8%; p = 0.041) observed for the LM and POC segment compared to the dMB. Significantly malapposed stent struts (>400 μm) were less likely to be covered at follow-up, than struts with a measured strut to vessel wall distance of <400 μm (15.4 ± 21.6 vs. 24.8 ± 23.9%; p = 0.011). Neoatherosclerosis was observed in 5 (33.3%) and restenotic neointimal hyperplasia (NIH) in 2 (13.3%) patients, requiring PCI in 33.3% of patients. Conclusions: Long-term OCT examination of DES implanted during primary PCI for culprit ULM lesions demonstrated high rates of incomplete strut coverage, late malapposition, and high subclinical DES failure rates. These negative OCT results highlight the need for image optimization strategies during primary PCI to improve DES-related long-term outcomes.

Mental health in children admitted with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): a follow-up study at 6 months of the Swissped-RECOVERY trial

BackgroundPIMS-TS presents with features considered to pose a risk for the development of unfavourable long-term mental health outcomes which haven’t been prospectively investigated. These include neurological symptoms (headache, confusion, and delirium), systemic inflammation, and critical illness requiring PICU support. Therefore, we set out to investigate mental health at 6-month follow-up in patients recruited into Swissped-RECOVERY trial.MethodsThis is a pre-planned analysis of the Swissped-RECOVERY trial (clinicaltrial.gov, NCT 04826588) investigating intravenous immunoglobulins versus intravenous methylprednisolone in patients with PIMS-TS. Mental health was assessed 6 months after hospital discharge using the Strength and Difficulties Questionnaire (SDQ), leading to a score concerning mental well-being (total score scale 0–40 points, subdomains 0–10 points). At population level it is expected that 80% of children belong to the normal, 10% to the borderline, and 10% to the abnormal band of the SDQ scores.FindingsSeventy-five patients were included, 66 (88%) parent-reported and 26 (78.8%) self-reported SDQs were returned. The median total difficulty score was 7.0 [4.0, 11.8] for parent-reported and 11.0 [7.0, 14.8] for self-reported SDQ. The total difficulty score was borderline or abnormal in 12/58 (20.7%) of parent-reported and 7/26 (26.9%) of self-reported SDQs. Emotional problems were reported borderline or abnormal in 19% and 27% of the parent- and self-reported SDQ, respectively, and for hyperactivity/inattention 21% and 27%, respectively.ConclusionEmotional problems and hyperactivity/inattention appeared to be the pressing concerns. Potential interference with daily activities such as home life, friendship, etc., makes early identification important to ensure adequate support.Trail registrationClinicalTrials.gov, ID NCT04826588, https://clinicaltrials.gov/study/NCT04826588.

Perspectives on the Use of Echinocandins in the Neonatal Intensive Care Unit.

The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile.

Prognostic value of morphology and hemodynamics in moyamoya disease for long-term outcomes and disease progression

To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p < 0.05). High rWSS at the terminal ICA and diabetes mellitus were identified as independent predictors of unfavorable long-term outcomes [OR = 3.039(1.191–7.754), p = 0.020; OR = 3.164(1.141–8.723), p = 0.027, respectively]. ROC analysis demonstrated that predictive models incorporating rWSS improved AUC values, with the highest AUC in Model 2 (AUC = 0.889). High rWSS was significantly associated with future TIA and stroke events (p = 0.032). We speculated that high rWSS and diabetes mellitus were independent risk factors for unfavorable long-term outcomes in patients with MMD. rWSS and morphological parameters are crucial for predicting MMD progression and understanding its pathogenesis.

Machine learning-based prediction of new onset of atrial fibrillation after mitral valve surgery

Abstract Background New-onset postoperative atrial fibrillation (nPOAF) is a common complication after cardiac surgery (30–50%), being associated with unfavorable long-term outcomes. Using the Society of Thoracic Surgeons National Adult Cardiac Database, we used machine learning (ML) to predict nPOAF and related 30-day outcomes following mitral valve (MV) surgery. A total of 27,856 MV operations were performed at 910 centers between 7/1/2017 and 6/30/2020 on patients without AF or a prior permanent pacemaker. The primary endpoint was nPOAF postoperatively. ML techniques utilized included penalized logistic regression, gradient boosting, decision trees, and random forests. Results The overall incidence of nPOAF was 35.4% and that of new pacemaker insertion was 5.6%. Patients who developed nPOAF were older (67 ± 10 vs 60 ± 13 years), had more mitral valve stenosis (14.1% vs 11.7%), and hypertension (72.1% vs 63.3%). They underwent more mitral valve replacement (39.1% vs 32.7%) and coronary artery bypass grafting (23.9% vs 16%). For predicting nPOAF, ML methods offer sensitivity, specificity and precision superior to logistic regression. The accuracy rate was identical with penalized and non-penalized logistic regression (0.672). Conclusions Predicting nPOAF and its short-term sequelae following MV surgery remains highly challenging. Machine learning methods offer a moderate degree of improvement in predicting nPOAF even in large national-level studies, in the absence of multi-modal data, such as real-time wearables data, electrocardiograms, heart rhythm monitoring, or cardiac imaging.

Long-term outcomes of 1,989 immediate implant-based breast reconstructions: an analysis of risk factors for failure and revision surgery.

Nipple- or skin-sparing mastectomy and immediate implant-based breast reconstruction (IBR) is potentially associated with long-term unfavorable outcomes such as revision surgery and reconstruction failure. This large patient cohort study aimed to provide long-term data on the incidence of these outcomes and identify predictive risk factors. Between 2012 and 2019 1,989 mastectomies with IBR were performed in 1,512 women in our institute. A direct-to-implant (DTI) method was used in 93% and a two-staged method with tissue-expander in 7%. Logistic regression analysis was used to identify patient- and treatment-related risk factors associated with revision surgery or reconstructive failure. Mean follow-up was 62.2 months. IBR failed in 6.7% of all breasts, thus a breast was present in 93.3%. Age older than 44 years old yielded a 2.6- and radiotherapy a 1.7-fold increased risk for reconstruction failure. Revision surgery was performed in 60% of all breasts. Mean number of revisions of all IBRs is 1.2 (range, 0-8; SD 1.37). Factors associated with significant higher rates of revision surgeries were age>44 years (OR=1.23), smoking (OR=1.53), specimen weight>492 grams (OR=1.39), implant volume>422 grams (OR=1.95) and radiotherapy (OR=1.51). Nipple preservation was protective for both outcomes (OR=0.71 and OR=0.42, respectively). DTI did not require any surgical revision in 43%. Despite the necessity of revision surgery in the majority of IBRs, nearly half of the breasts did not require any revision surgery, and long-term reconstruction failure rates are extremely low. Therefore, IBR should be offered to all eligible women undergoing mastectomy while understanding the risks.

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease.

Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.

Genetic susceptibility to temporomandibular joint involvement in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Temporomandibular joint (TMJ) is among the most commonly affected joints in JIA patients. When JIA involves the TMJ, it may affect condylar growth in the joint; therefore, JIA patients are at risk of unfavourable long-term outcomes from associated joint damage. If undetected, TMJ involvement can lead to various functional disabilities such as reduced mandibular mobility and disorders of the mastication muscles. Limitations in sagittal and vertical mandibular growth can result in micrognathia and anterior open bite with aesthetic and functional restrictions. Genetic factors may play a role in determining which individuals are more prone to develop TMJ disorders or in predicting the severity of the disease process. Therefore, we applied a GWAS approach to identify loci associated with TMJ involvement in a sample of Estonian patients with JIA. Our aim was to address the potential role of genetic susceptibility factors in TMJ-JIA, a condition not previously studied in this context. The case group consisted of 55 JIA patients with TMJ involvement and 208 patients without TMJ involvement comprised the control group. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. Imputation was performed using a nationwide reference panel obtained of 2240 individuals whose data were obtained from the Estonian Biobank. We identified six loci as being associated with the risk of TMJ-JIA in Estonian JIA patients. The strongest associations were identified at CD6 rs3019551 (P = 3.80 × 10-6), SLC26A8/MAPK14 rs9470191 (P = 6.15 × 10-6), NLRP3 rs2056795 (P = 8.91 × 10-6) and MAP2K4 rs7225328 (P = 1.64 × 10-5). This study provides first insights into the risk-associated loci between JIA and its manifestation in the TMJ. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that render the TMJ susceptible to involvement by JIA in Estonian patients.

Unfavorable neurological long-term outcome despite eTICI 3 – What are the predictors?

PurposeInterventional stroke therapy has become standard treatment for patients with acute ischemic strokes. Complete reperfusion (eTICI 3) portrays the best possible technical outcome. The purpose of this study was to determine possible predictors for an unfavorable neurological long-term outcome (mRS 3–6) despite achieving the best possible treatment success. MethodsWe evaluated 122 patients with stroke in the anterior circulation and complete reperfusion after mechanical thrombectomy (MT) between May 2010 and March 2020. We performed a binary logistic regression analysis with patient baseline data, stroke severity, comorbidities, premedication and treatment information as independent variables. Results50 of the 122 patients included in our study showed a poor clinical outcome after 90 days (41 %). Multivariable logistic regression analysis showed that older age (p = 0.033), higher admission NIHSS (p=0.009), lower admission ASPECTS (p=0.005), a pre-existing cardiovascular disease (p=0.017), and multiple passes for complete reperfusion (p=0.030) had an independent impact on unfavorable outcome. ConclusionsOlder age, higher NIHSS upon admission, lower ASPECTS upon admission, cardiovascular comorbidities and multiple passes for complete reperfusion are predictors for poor neurological long-term outcome despite complete reperfusion.

Immunosuppressives discontinuation after renal response in lupus nephritis: predictors of flares, time to withdrawal and long-term outcomes.

The optimal duration of immunosuppressive (IS) treatment for lupus nephritis (LN) remains uncertain. We assessed the prevalence and predictors of IS tapering and discontinuation (D/C) in LN patients. Data from 137 inception cohort LN patients were analyzed. We examined determinants of flares during tapering and after IS D/C, D/C achievement and time to D/C, and adverse long-term outcomes applying logistic and linear regression models. IS tapering was attempted in 111 (81%) patients, and D/C was achieved in 67.5%. Longer time to achieve complete renal response (CR) (OR : 1.07, p= 0.046) and higher SLEDAI-2K at tapering initiation (OR : 2.57, p= 0.008) were correlated with higher risk of renal flares during tapering. Persistent hydroxychloroquine use (≥2/3 of follow-up) (OR : 0.28, p= 0.08) and lower SLEDAI-2K 12 months before IS D/C (OR : 1.70, p= 0.013) decreased the risk of post-D/C flares. Adverse outcomes (>30% eGFR decline, chronic kidney disease, end-stage renal disease, death) at the end of follow-up (median124 months) were more frequent in patients with flares during IS tapering (53% vs 16%, p< 0.0038) but did not differ between IS D/C achievers and non-achievers. In proliferative LN, differences mirrored those in entire cohort, except for time to D/C, which occurred 20 months earlier in membranous vs proliferative LN (β-coef=-19.8, p= 0.014). Earlier CR achievement and lower SLEDAI-2K at tapering initiation prevent flares during IS tapering, while persistent hydroxychloroquine use and lower SLEDAI-2K 12 months before IS D/C prevent post-D/C flares. Flares during tapering increase the risk of unfavorable long-term outcomes. Earlier IS D/C is feasible in membranous LN.

Increased Donor Organ Size and Age is Associated with Reduced Survival in Female Lung Transplant Recipients

BackgroundOrgan selection in lung transplantation (LTx) is still controversial. We here analyze the impact of mismatches in size, age, and gender on early and long-term outcome after LTx. MethodsRetrospective analysis of donor and recipient characteristics of patients who underwent double lung transplantation (DLTx) between 03/2003 and 12/2021. Statistical analysis was performed using SPSS and GraphPad software. Results203 patients were included (94 female and 109 male). In the whole cohort, oversizing donor organs 10%-20% compared to the recipients’ predicted total lung capacity (pTLC) led to a decreased incidence of severe primary graft dysfunction (PGD2/3) (15% vs. 41%, p=0.03), and further oversizing >20% was associated with reduced long-term survival (HR 2.33, p=0.011). Analysing donor and recipient age, we found that increased donor age correlated with reduced long-term survival (p=0.013). In this cohort, female recipients received older organs (median 57 vs. 46 years, p=0.0003) and had a higher incidence of >20% oversizing (13% vs. 4%, p=0.019) of donor lungs which resulted in a significantly reduced long-term survival (p=0.02) compared to male recipients. Median LAS scores were similar in both groups. ConclusionMismatch of donor age and size can be important for organ function and survival in lung transplant recipients. Particularly female recipients seem to have a higher risk for unfavourable long-term outcome when transplanting organs of increased size and age. Multicentre studies are warranted to further address this question.

The Inhibition of RXRα and RXRβ Receptors Provides Valuable Insights for Potential Prostate Cancer Treatment, in silico Molecular Docking and Molecular Dynamics Studies.

Prostate cancer has emerged as a widespread health concern, with systemic inflammation believed to substantially contribute to its development and progression. The presence of systemic inflammatory responses has been established as an independent predictor of unfavorable long-term outcomes in prostate cancer patients. The goal of this study is to inhibit RXRα and RXRβ receptors, which are involved in prostate cancer, with Luteolin, Formononetin, and Kaempferol, with varying success. Retinoid X receptors (RXRs) hold crucial roles within the nuclear receptor (NR) superfamily, and compelling evidence from preclinical studies underscores the therapeutic potential of targeting RXRs for treating neurodegenerative and inflammatory conditions. Consequently, the ability to regulate and modulate RXRs using phytoestrogen ligands, Formononetin, Kaempferol, and Luteolin, assume paramount importance in treatment strategies. The comprehensive in silico findings of this study vividly demonstrate the remarkable efficacy of Luteolin in inhibiting and modulating RXRα and RXRβ, while Formononetin emerges as a notably potent suppressor of RXRβ. Kaempferol, as the third compound, also exhibits commendable inhibitory attributes, although its impact is slightly less pronounced compared to the other two. These findings highlight the notable binding and inhibition capabilities to RXRα and RXRβ, offering valuable insights for potential prostate cancer treatment avenues warranting further exploration through in vitro and in vivo analyses.

The Association of Heterozygous p.R4810K of RNF213 and Long-Term Unfavorable Outcomes after Encephaloduroarteriosynangiosis in Chinese Pediatric Patients with Moyamoya Disease

Background. Previous studies have established that heterozygous mutation for the p.R4810K variant can influence the severity of the clinical phenotype in patients with moyamoya disease (MMD) at disease onset. However, the relationship between the p.R4810K variant and the clinical phenotype of long-term unfavorable outcomes in Chinese pediatric patients remains unclear. Objectives. The primary aim of this study was to examine the association of heterozygous p.R4810K of RNF213 and long-term unfavorable outcomes after encephaloduroarteriosynangiosis (EDAS) in Chinese pediatric patients with MMD. Method. In this retrospective cohort study, we included 259 pediatric patients with MMD who possessed the known p.R4810K genotype. These individuals underwent EDAS along with genotyping analysis for p.R4810K via a TaqMan probe and the QuantStudio 6 Flex Real-Time PCR System. Subsequently, we evaluated their long-term outcomes. The variables we assessed were age at diagnosis, gender, p.R4810K genotypes, initial modified Rankin scale (mRS), clinical manifestations (such as hemorrhage and ischemia), posterior cerebral artery (PCA) involvement combined with angiographic stage, and their history of risk factors like hyperlipidemia and hyperhomocysteinemia. Furthermore, we scrutinized long-term unfavorable outcomes using both univariate analyses and multivariate logistic regression to identify independent predictive factors. Results. This study enrolled 259 Chinese pediatric patients with MMD, which included both newly and previously diagnosed cases, who underwent EDAS. The cohort comprised 130 male participants (50.19%) and 129 female participants (49.81%), with a median onset age of 8 years (median, IQR: 6-12 years). Among these patients, homozygous mutations were exceptionally rare, identified in only 4 individuals (1.54%), while the prevalence of heterozygous mutations was relatively higher, observed in 85 children (32.82%). The multivariate logistic regression showed that several factors were significantly associated with long-term unfavorable outcomes: older age at diagnosis (OR, 0.82 [95% CI, 0.7-0.96], P=0.014), onset with hematoma (OR, 12.76 [95% CI, 1.52-106.89], P=0.019), initial mRS (OR, 24.53 [95% CI, 6.51-92.41], P&lt;0.001), perioperative infarction (OR, 22.16 [95% CI, 1.45-337.96], P=0.026), and infarction during follow-up (OR, 14.5 [95% CI, 2.04-103.12], P=0.008). Furthermore, the cumulative incidence of initial infarction suggested that pediatric patients with homozygous or heterozygous mutations typically present at a younger age and exhibit a higher incidence of initial infarction compared to those carrying wild-type genotypes. Conclusions. The study suggests that the p.R4810K variant is associated with the onset age of MMD in Chinese pediatric patients, potentially impacting long-term outcomes. Surprisingly low recurrent stroke rates were observed across all genotypes, including homozygous individuals for the pathogenic variant, indicating that nongenetic factors may also play a role in the course and outcomes of MMD in this population.

Study on clinical features and factors related to long-term outcomes of antibody-negative autoimmune encephalitis.

To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among antibody-negative AE. Patients diagnosed with antibody-negative AE were recruited from January 2016 to December 2022 at the Second Xiangya Hospital of Central South University. The study assessed the long-term outcomes of antibody-negative AE using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Predictors influencing long-term outcomes were subsequently analyzed. External validation of RAPID scores (refractory status epilepticus [RSE], age of onset ≥60 years, ANPRA [antibody-negative probable autoimmune encephalitis], infratentorial involvement, and delay of immunotherapy ≥1 month) was performed. In total, 100 (47 females and 53 males) antibody-negative AE patients were enrolled in this study, with approximately 49 (49%) experiencing unfavorable long-term outcomes (mRS scores ≥3). Antibody-negative AE was subcategorized into ANPRA, autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Psychiatric symptoms were prevalent in LE and ANPRA subtypes, while weakness and gait instability/dystonia were predominant in the ADEM subtype. Higher peak CASE scores (odds ratio [OR] 1.846, 95% confidence interval [CI]: 1.163-2.930, p = 0.009) and initiating immunotherapy within 30 days (OR 0.210, 95% CI: 0.046-0.948, p = 0.042) were correlated with long-term outcomes. Receiver operating characteristic (ROC) analysis returned that the RAPID scores cutoff of 1.5 best discriminated the group with poor long-term outcomes (sensitivity 85.7%, specificity 56.9%). The ANPRA subtype exhibited poorer long-term outcomes compared to LE and ADEM subtypes, and early immunotherapy was crucial for improving long-term outcomes in antibody-negative AE. The use of RAPID scoring could aid in guiding clinical decision making.

Impact of SWCNTs and CMCS on efficacy of anastomosis and optical properties in vivo during laser biological tissue soldering

In order to improve the mechanical properties of skin tissue incision, enhance laser absorption efficiency, further shorten healing time and reduce skin fibrosis tendency, this study investigated the effects of CMCS or SWCNT combined with 25 % BSA and 0.4 % ICG on laser tissue welding. Nd:YAG pulsed laser was used for wound closure test on live rats with an energy density of 67.3 J/cm2 and linear scanning of skin incisions. The effects of different types and concentrations of biological dressings on wound closure were tested at different sites. The results showed that biocompatible dressings containing CMCS and SWCNTs had a significant effect in promoting wound healing after laser welding. After laser welding, the tensile strength of the control group without CMCS or SWCNTs was only between 6.5 and 9.8 N/cm2, while that with CMCS reached as high as 26.5 N/cm2. Macroscopic morphology analysis showed that components such as CMCS and SWCNTs could significantly shorten healing time from 14 days to 9–10 days. Optical performance tests demonstrated that a combination of 5 %CMCS and 4 %SWCNTs can significantly increase skin's absorption coefficient for laser photons up to7-8 Lg-1cm−1 and reduce photon diffuse reflectance. HE and Masson staining revealed that when internalized by dressing containing 0.4 %SWCNTs, nanocarbon particles promoted collagen skeleton regeneration but increased fibrosis tendency after 14 days post-laser welding, resulting in unfavorable long-term healing outcomes. However, the combination of CMSC with SWCNTs can significantly improve incision mechanical properties, laser photon absorption rate, and shorten healing time while reducing scar proliferation tendencies.

A Comprehensive Examination of Clinical Characteristics and Determinants of Long-Term Outcomes in Pediatric Cerebral Sinus Venous Thrombosis

BackgroundTo analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT). MethodsThis is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children's Hospital. ResultsA total of 183 children (male: 62.3%) with CSVT were included. The average presenting age was 7.7 years (S.D.: 5.6). The mean follow-up duration was 33.7 months (S.D.: 38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological examination findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), and intracranial hemorrhage without infarction (5.5%). The most common site of thrombosis was the superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low-molecular-weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included head and neck infections, malignancy (other than hematologic), cardiac disease, and recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only; and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome. ConclusionsCSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion and early and appropriate management of pediatric CSVT is imperative.

Which magnetic resonance imaging feature is associated with treatment response in perianal fistulizing Crohn's disease?

Perianal fistulae are disabling complications of Crohn's Disease. Magnetic resonance imaging features could predict treatment response. This study aimed to determine which magnetic resonance imaging features were predictive of long-term clinical outcome in real life. Consecutive patients with magnetic resonance imaging performed in a tertiary center were retrospectively analyzed. Clinical outcome was defined as a need for surgical drainage of perianal fistulae or hospitalization. Clinical data and magnetic resonance imaging features (MAGNIFI-CD and Van Assche indices, degree of fibrosis) were studied. Fifty-two patients were included between 2016 and 2019 with a mean follow-up of 38months [29;48]. A higher MAGNIFI-CD index (17/25 versus 11/25; p < 0.01) was associated with an unfavorable long-term clinical outcome. The MAGNIFI-CD index showed an area under the curve of 0.74 (p = 0.006) to predict the clinical outcome of perianal Crohn's disease, compared to 0.67 (p < 0.05) for the Van Assche index. At a threshold of 13 for the MAGNIFI-CD index, sensitivity was 75% (CI95% [59%; 86%]) and specificity was 69% (CI95% [44%; 86%]). No association was found between the degree of fibrosis and clinical outcome, but the association of a high degree of fibrosis (≥ 80%) and of a low MAGNIFI-CD index (≤ 13) was predictive of clinical outcome (p < 0.01). The MAGNIFI-CD index could be used to predict clinical outcome in perianal Crohn's disease. In combination with a high degree of fibrosis, a low MAGNIFI-CD index, may help to identify patients with the best prognosis.

Abstract HUP3: Neighborhood Deprivation and Functional Outcomes Following Ischemic Stroke

Introduction: The association between neighborhood deprivation and risk of disease is well-documented. However, the role of neighborhood deprivation in long-term outcomes following acute brain injury remains understudied. We tested the hypothesis that neighborhood deprivation leads to unfavorable long-term functional outcomes following acute ischemic stroke (AIS). Methods: We conducted a nested study within the Yale Longitudinal Study of Acute Brain Injury, a prospective study which follows patients with acute brain injury admitted to the Yale Health System. The present study focused on AIS survivors and assessed neighborhood deprivation using the Area Deprivation Index (ADI), a metric that uses 9-digit zip codes to rank neighborhoods based on income, employment, education, and housing quality. Patients were stratified into tertiles based on their ADI, designated as low, intermediate, or high deprivation. Functional outcomes were evaluated using the modified Rankin Scale at one-year post-stroke, dichotomized into favorable (scores 0-2) and unfavorable (scores 3-6). Our analysis employed multivariable logistic regression for adjusted analyses. Results: Among 2,540 AIS patients enrolled between 2018 and 2021, 2,164 patients had zip code and outcomes data (mean age 69 years, 48% female, 7.5% Black, 7.7% Hispanic). The one-year unadjusted risk of poor outcomes was 35%, 40% and 46% for patients residing in neighborhoods with low, intermediate, and high deprivation, respectively (unadjusted p=0.001). These findings remained significant in multivariate analyses that controlled for confounding factors: compared to patients living in neighborhoods with low deprivation, those living in areas with intermediate and high deprivation had 44% (OR 1.44, 95% CI 1.11-1.86) and 107% (OR 2.07, 95% CI 1.58-2.72) greater risk of unfavorable outcomes (test-for-trend p&lt;0.001). Conclusion: Our study, focusing on survivors of AIS participating in a prospective acute brain injury study, underscores the connection between neighborhood deprivation and an elevated risk of unfavorable outcomes. We validate the utility of the ADI as a valuable analytical tool for evaluating neighborhood deprivation as a composite for several social determinants of health.