High Risk Of Failure Research Articles

Machine Learning and Optical-Coherence-Tomography-Derived Radiomics Analysis to Predict the Postoperative Anatomical Outcome of Full-Thickness Macular Hole.

Full-thickness macular hole (FTMH) leads to central vision loss. It is essential to identify patients with FTMH at high risk of postoperative failure accurately to achieve anatomical closure. This study aimed to construct a predictive model for the anatomical outcome of FTMH after surgery. A retrospective study was performed, analyzing 200 eyes from 197 patients diagnosed with FTMH. Radiomics features were extracted from optical coherence tomography (OCT) images. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained and evaluated. Decision curve analysis and survival analysis were performed to assess the clinical implications. Sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC) were calculated to assess the model effectiveness. In the training set, the AUC values were 0.998, 0.988, and 0.995, respectively. In the test set, the AUC values were 0.941, 0.943, and 0.968, respectively. The OCT-omics scores were significantly higher in the "Open" group than in the "Closed" group and were positively correlated with the minimum diameter (MIN) and base diameter (BASE) of FTMH. Therefore, in this study, we developed a model with robust discriminative ability to predict the postoperative anatomical outcome of FTMH.

The influences of microstructural length scale on the tensile properties and deformation mechanisms of Sn-3.0Ag-0.5Cu solder alloys

Optimizing microstructures remains critical for improving the reliability of Pb-free solder joints, especially in applications with high failure risks. The mechanical properties of Sn-3.0Ag-0.5Cu (SAC305) solder alloys is intricately linked to the length scale of the initial microstructure. This paper investigates the effects of microstructure refinement on uniaxial tensile properties, nanomechanical response, plastic deformation, and fracture using directional solidification techniques. The findings demonstrate that controlling the microstructure can effectively enhance mechanical properties, dynamic recrystallization, and intragranular deformation in SAC305 alloys. Furthermore, the study explores heterogeneous plastic deformation and the interaction between eutectic intermetallics and β-Sn. These results offer valuable insights for optimizing microstructures to achieve superior solder joint performance.

Cohort profile: the PRIMETIME 1 (PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy) cohort – a longitudinal Danish nationwide study of individuals with diabetes and a performed kidney biopsy

PurposeIndividuals with diabetes and chronic kidney disease are at high risk of kidney failure, cardiovascular events and premature mortality and more research is warranted to further improve the prevention and...

The LUSBI Protocol (Lung Ultrasound/BREST Score/Inferior Vena Cava)-Its Role in a Differential Diagnostic Approach to Dyspnea of Cardiogenic and Non-Cardiogenic Origin.

Background and Objectives: PoCUS ultrasound applications are widely used in everyday work, especially in the field of emergency medicine. The main goal of this research was to create a diagnostic and therapeutic protocol that will integrate ultrasound examination of the lungs, ultrasound measurements of the inferior vena cava (assessment of central venous pressure) and BREST scores (risk stratification for heart failure), with the aim of establishing a more effective differential diagnostic approach for dyspneic patients. Materials and Methods: A cross-sectional study was conducted in the emergency medicine department with the educational center of the community health center of Banja Luka. Eighty patients of both sexes were included and divided into experimental and control groups based on the presence or absence of dyspnea as a dominant subjective complaint. Based on the abovementioned variables, the LUSBI protocol (lung ultrasound/BREST score/inferior vena cava) was created, including profiles to determine the nature of the origin of complaints. The biochemical marker of heart failure NT pro-BNP served as a laboratory confirmation of the cardiac origin of the complaints. Results: The distribution of NT pro BNP values in the experimental group showed statistically significant differences between individual profiles of the LUSBI protocol (p < 0.001). Patients assigned to group B PLAPS 2 had significantly higher average values of NT pro-BNP (20159.00 ± 3114.02 pg/mL) compared to other LUSBI profiles. Patients from the experimental group who had a high risk of heart failure according to their BREST scores also had a significantly higher average maximum expiratory diameter compared to those without heart failure (p = 0.004). A statistically significant difference (p = 0.001) in LUSBI profiles was observed between the groups of patients divided according to CVP categories. Conclusion: The integration of the LUSBI protocol into the differential diagnosis of dyspnea has been shown to be very effective in confirming or excluding a cardiac cause of the disease in patients.

Abstract A014: Protein-informed gene methylation signatures to predict treatment response and outcomes in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer with dismal outcomes. We need new biomarkers to optimize the limited treatment combinations used in current clinical practice. Many machine-learning models have been presented based on mutational or transcriptome data claiming to predict outcomes. Still, they do not provide actionable targets (genes) that could improve treatment response. Moreover, DNA-methylation changes that influence gene/protein expression have been explored for this purpose. From the literature, we curated a 122-gene panel (January 1970 to April 2024) constructed on the proteins with preclinical (on cell lines or mouse models) or clinical (tissue-based studies) evidence suggesting their individual roles in influencing response to drugs often used in managing PDA such as gemcitabine (Gem), nab-paclitaxel, oxaliplatin, 5-fluorouracil, irinotecan, and cisplatin. We hypothesized that methylation changes in these genes are surrogates for gene/protein expression and tested their clinical significance in The Cancer Genome Atlas (TCGA) PDA population (n=184). The goal was to develop methylation signatures composed of specific cytosines followed by guanine residue (CpG) sites that aid in identifying patients at high risk of treatment failure and poor outcomes. We used elastic net multivariate analysis to calculate survival and plot Kaplan Meier plots based on our gene panel. The alpha (α) used for this script was calculated based on the lowest mean error and the minimum lambda (λ) value accordingly for each iteration (100 iterations to calculate the best values for α and λ). Our analysis yielded 28 methylation signatures that could identify high-risk PDA patients with poor overall survival (OS). The number of CpG sites in these signatures ranged from 1 to 1933. The differences in OS for these signatures were better than those available in the literature. The best signature had 18 CpG sites (17 months (m) vs. not evaluable) followed by a 53-CpG site signature (16 m vs. 67m) and a 6-CpG site signature (17m vs. 67m). A signature with the highest CpG sites (1933) was not better than those with smaller ones (16m vs. 21m). Multiple signatures had &amp;gt;1 CpG sites from one gene. Early growth response 1 (EGR1) coding the KCNH2 gene has featured in most signatures. One CpG site in this gene had a clinically significant prognostic value (15m vs. 30m). Other frequently featured genes were CCDC85A, EGFR, SST, and HMGA1. The main drawbacks for this study were that Gem-related genes (&amp;gt; 60) dominated the panel, and those with Gem treatment dominated the patient population. This panel should be further refined to make it more relevant to current clinical practice. We provide preliminary evidence suggesting the clinical significance of our panel and lay the foundation for future studies that would enable us to personalize prognostication and treatment selection in PDA patients. Our work can provide novel therapeutic targets that, alone or in combination with chemotherapy, can improve the outcomes for PDA. Citation Format: Ashish Manne, Harshitha Puram, Deepak Sherpally, Sravan Jeepalyam, Upender Manne. Protein-informed gene methylation signatures to predict treatment response and outcomes in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A014.

Selection of dialysis methods for end-stage kidney disease patients with diabetes.

The increasing prevalence of diabetes has led to a growing population of end-stage kidney disease (ESKD) patients with diabetes. Currently, kidney transplantation is the best treatment option for ESKD patients; however, it is limited by the lack of donors. Therefore, dialysis has become the standard treatment for ESKD patients. However, the optimal dialysis method for diabetic ESKD patients remains controversial. ESKD patients with diabetes often present with complex conditions and numerous complications. Furthermore, these patients face a high risk of infection and technical failure, are more susceptible to malnutrition, have difficulty establishing vascular access, and experience more frequent blood sugar fluctuations than the general population. Therefore, this article reviews nine critical aspects: Survival rate, glucose metabolism disorder, infectious complications, cardiovascular events, residual renal function, quality of life, economic benefits, malnutrition, and volume load. This study aims to assist clinicians in selecting individualized treatment methods by comparing the advantages and disadvantages of hemodialysis and peritoneal dialysis, thereby improving patients' quality of life and survival rates.

Implant-Supported Vertical Soft Tissue Augmentation for Severe Hard and Soft Tissue Deficiencies at Malpositioned Implants: A Case Report of a Mucogingival and Restorative Approach.

The management of severe mucogingival deformities surrounding malpositioned implants represents a complex issue with a high risk of aesthetic failure. The present case report describes a mucogingival and restorative approach for the treatment of severe localized peri-implant tissue deficiencies with interproximal bone loss combined with an interproximal gingival recession on the adjacent natural tooth. This consists of maintaining a non-restorable malpositioned implant, submerging it through one or multiple vertical soft tissue augmentations, according to the defect severity, and delivering a tooth supported bridge involving the adjacent natural teeth. The step-by-step surgical technique adopted for implant submergence and vertical soft tissue grafting, as well as the subsequent surgical and prosthetic interventions, are described, presenting results at 5 years from implant submergence and 3 years from prosthetic finalization.

Hydrocephalus: A Review of Etiology-Driven Treatment Strategies.

Hydrocephalus is a broad term usually understood as cerebrospinal fluid (CSF) accumulation resulting in cerebral ventricular system expansion. The production of CSF is by the choroid plexus in lateral ventricles, flowing between the third and fourth ventricles and eventually to the subarachnoid space. It is critical for proper neuronal function. Hydrocephalus is a neurological pathology linked to high morbidity from neurocognitive and motor impairment. It is classified as either communicating or non-communicating. Communicating hydrocephalus is understood as a deficit at cranial arachnoid villi and granulation absorption sites. However, there has been evidence that extracranial lymphatic vessels in the ethmoid bone region also play a role, as indicated by decreased lymphatic absorption in rat models of hydrocephalus. Treatment typically involves surgical shunt placement or endoscopic third ventriculostomy (ETV) technique with or without choroid plexus cauterization (CPC). These surgical interventions have high failure risks and complications that require re-intervention, further increasing morbidity and mortality risks. To date, there are few nonsurgical treatment strategies, but many have proved limited benefit, and many patients still require surgery. This analysis lays out the typical treatments and explores new, innovative interventions by highlighting the active role of brain parenchymal tissue in the pathogenesis of hydrocephalus.

Persistent Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Rectal Cancer

Patients with locally advanced rectal cancer and persistent lymph node metastases (PLNM) after neoadjuvant treatment are at high risk of developing locoregional and distant metastasis, yet optimal postsurgical treatment of these patients is limited. To analyze the association of PLNM with pretreatment clinical parameters, intensity of neoadjuvant treatment, and long-term oncological outcomes. This cohort study is a post-hoc analysis of 3 randomized clinical trials (Surgical Oncology Working Group of Germany [CAO], Radiological Oncology Working Group of Germany [ARO], and Working Group for Internal Oncology in the German Cancer Society [AIO]) conducted in Germany in 1994, 2004, and 2012 that included 1948 patients with locally advanced rectal cancer recruited between February 1995 and January 2018. Statistical analysis was conducted between September 2023 and February 2024. Receiving preoperative fluorouracil-based chemoradiotherapy (CRT, comprising the preoperative group of CAO/ARO/AIO-94 and the control group of CAO/ARO/AIO-04), fluorouracil-based CRT plus oxaliplatin (experimental group of CAO/ARO/AIO-04), or total neoadjuvant treatment (TNT) with fluorouracil-based CRT plus oxaliplatin with induction or consolidation leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin chemotherapy within the CAO/ARO/AIO-12 trial. The associations of PLNM with clinical parameters, intensity of neoadjuvant treatment, and cumulative incidences of LR, DM, and overall survival were assessed. A total of 1888 patients (1333 male participants [70.6%]; median [range] age, 62 [19-84] years) with locally advanced rectal adenocarcinoma (clinical tumor stage 3 to 4 and/or clinically node-positive) treated within 3 consecutive clinical trials were analyzed. A total of 522 (29%) experienced PLNM; 378 had lymph node stage (ypN) 1 (20%) after neoadjuvant treatment (ypN) 1 (20%), and 174 had ypN2 (9%). Age, clinical T-stage, N-stage, grading, carcinoembryonic antigen levels, and time interval from completion of CRT to surgery were significantly associated with PLNM, whereas sex and tumor location were not. The percentage of patients with ypN2 stage was almost halved after TNT (18 of 293 patients [6%]) compared with patients treated with fluorouracil-based CRT (114 of 1009 patients [11.3%]; χ26 = 16.693; P = .01). After a median (IQR) follow-up of 54 (37-62) months, 5-year overall survival was 86.1% (95% CI, 83.9%-88.4%) for ypN0, 74.0% (95% CI, 83.9%-88.4%) for ypN1, and 43% for ypN2 (95% CI, 35.4%-52.2%) (P < .001). The 5-year cumulative incidences of locoregional and distant metastases were, respectively, 3% (95% CI, 2.1%-4.2%) and 20% (95% CI, 18%-23%) for ypN0, 6% (95% CI, 3.4%-8.8%) and 40% (95% CI, 34%-46%) for ypN1, and 19% (95% CI, 13%-26%) and 72% (95% CI, 63%-79%) for ypN2 (both P < .001). In this cohort study, PLNM unmasked an unfavorable phenotype of rectal cancer at high risk for treatment failure. More aggressive adjuvant treatment might be considered; however, risk-adapted surveillance strategies and early recurrence-directed surgery, if feasible, are important strategies in this group of patients with CRT- and/or chemotherapy-resistant disease.

A System Architecture for Early Wilt Detection in Hydroponic Crops: An Implementation and Assessment

Abstract Hydroponic farming systems have a high risk of failure if the disaster is not mitigated and responded to quickly. Hydroponic plants only rely on mineral water that flows through their roots as a source of life; thus, any malfunction will have an immediate impact on the plant. If plant wilting is not recognized and not treated quickly, the plant will experience stress and have the potential to fail. To ensure that major disasters do not occur, an early warning mechanism is needed that can provide disaster information to farmers. In this study, an intelligent system architecture was built to detect premature wilt in hydroponic vegetable plants. It combines the capabilities offered by the OV2640 image sensor and ESP32-S system-on-chip, the Internet of Things, deep learning based on convolutional neural networks, and cloud computing to create a robust and low-cost remote plant condition monitoring solution. As a proof-of-concept, a prototype system is built, and performance tests are carried out to find out how robust and effective the proposed design is. Based on the results of the prototype test, it can be seen that the system built can run properly with an accuracy of wilting recognition of up to 90.90%, which was tested on samples of vertically grown mustard plants in a hydroponic greenhouse.

Numerical study on the motion characteristics of free fall lifeboats entering calm water and rough sea

As ocean engineering operations extend into deeper seas, the working environment becomes increasingly complex, making free fall lifeboats (FFLBs) more vital for maritime disaster rescues. Unlike traditional davit-launched lifeboats, FFLBs are propelled into the water at a specific velocity and angle, engaging in a complex motion process of launch, impact, submersion, and resurfacing. Therefore, to assess the safety of FFLBs, this paper regarding the lifeboat as a rigid body aims to investigate the six-degree-of-freedom motion characteristics of lifeboat entering the water with different entry angles θ and wave environment, with a specific focus on analyzing the primary causes of capsizing. The numerical simulations of water entry with various θ, wave heights H, and relative entry positions are carried out by combining large eddy simulation and overset mesh technology. The free surface is captured by the volume of fluid method, and the attitude change, acceleration change, motion trajectory, and free surface evolution law of lifeboats are analyzed. The findings suggest that lifeboats can enter calm water safely at θ of 20°–50° and maintain a stable posture. Moreover, in extreme conditions where θ is either 0° or 90°, there is a high risk of entry failure due to excessive vertical acceleration and poor motion attitude, respectively. Furthermore, when facing waves, lifeboats experience reduced horizontal displacement when entering at peak and downward zero point compared to calm water conditions, which poses challenges for avoiding potential dangers.

Blood urea nitrogen-to-albumin ratio independently predicts 30-day mortality in acute respiratory failure patients: a retrospective cohort study.

It is crucial to identify patients at high risk for acute respiratory failure (ARF) to provide appropriate and optimal clinical treatment. While previous studies have explored the use of prognostic biomarkers based on a combination of blood urea nitrogen (BUN) and albumin levels, no reports to date have evaluated its utility across a wide range of ARF etiologies in a large and diverse critical care population. Therefore, we aimed to ascertain the association between the BUN-to-albumin ratio (BAR) and mortality in these patients. Data recorded in the first 24 h following intensive care unit (ICU) admission, including demographics, vital signs, laboratory test results, comorbidities, and score systems were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A general additive model was used to determine whether there was a non-linear relationship between BAR and 30-day mortality. A multivariate Cox analysis was performed to measure the association between them. The study enrolled 9,734 patients with ARF. In comparison to survivors, non-survivors exhibited higher BAR [10.79 (6.25-18.81) vs. 7.35 (4.48-13.62), P<0.001]. The correlation between baseline BAR and 30-day all-cause mortality in patients with ARF was non-linear, with a significant inflection point (11.76 mg/g). The Kaplan-Meier curve demonstrated that ARF patients had higher 30-day all-cause mortality rates when they had higher BAR levels (>11.76 mg/g) with hazard ratio (HR) 1.54 [95% confidence interval (CI): 1.39-1.70]. A high BAR was linked to a higher risk of mortality in ARF patients. BAR is a straightforward and possibly useful prognostic biomarker for ARF.

Fibrin clot augmentation of high-risk meniscal repairs may result in clinical healing in up to 90% of cases

ObjectiveWhile meniscal repair is preferable to meniscectomy, some cases may be at higher risk of failure if repaired. Incorporating fibrin clot (FC) into the repair has been proposed to improve healing rates. The purpose of this study was to determine the failure rates, patient reported outcome measures (PROMs) and complications of FC augmented meniscal repair for cases considered to be at higher risk of failure. MethodsA retrospective case series of all patients undergoing FC augmented repair of isolated meniscus tears between January 2016 and September 2021 was undertaken. All cases were thought be at higher risk of failure; they included chronic, radial, complex, horizontal cleavage, and tears not in the red–red zone. Patients were excluded if they had a concomitant anterior cruciate ligament (ACL) reconstruction or if the repair was done through an open incision. The primary outcome was clinical failure defined as further repair or debridement. Secondary outcomes were PROMs and surgical complications. PROMs collected were Lysholm score, Knee injury and Osteoarthritis Outcome Score, Oxford Knee Score and the Tegner score. ResultsFifty one inside-out meniscal repairs using FC were performed in 50 patients (62% male). The mean age was 34 years (range 14–70). The median time from injury to repair was 122 days (range 4–1565). The medial meniscus was repaired in 63% of cases. Tear types included radial (31%) and complex (39%) and 71% of cases included repair of the white–white zone. 16% of cases were revision meniscal repairs. FC was used in 43% of isolated meniscal repairs during the study period. All patients were followed up to a median of 46 months (range 22–87 months). PROMs at a median of 30 months post-operatively showed statistically significant improvements. Five patients (10%) underwent further surgery for failure after median 21 months. Two patients (4%) reported sensory disturbance around their skin wounds, no other complications were reported. 13% of medial meniscal repairs failed, whereas only 5% of lateral meniscal repairs failed (p ​= ​0.4). ConclusionsFC augmented meniscal repair performed for tears considered to be at higher risk of failure may result in acceptably low rates of clinical failure. Level of evidenceLevel IV, case series.

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial

BackgroundPeople with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m2, kidney replacement therapy, and kidney or CV death) by 24%. ObjectivesThis prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. MethodsParticipants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. ResultsA total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment. ConclusionsSemaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153)

1234: UICC, but not, can identify high risk of locoregional failure as good as our multi-endpoint model

1234: UICC, but not, can identify high risk of locoregional failure as good as our multi-endpoint model

Progression of Heart Failure in People with Type 2 Diabetes in Germany: An Analysis Using German Health Insurance Claims Data.

Background: Individuals with type 2 diabetes (T2D) show high risk of heart failure (HF). Left ventricular ejection fraction is a major factor for disease progression. In Germany, no recent longitudinal data are available. Objectives: To (1) measure the proportion of individuals with T2D who acquire HF over 2 years and (2) categorize ejection fraction using routine data and an algorithm, and (3) understand progression of HF in 5-year follow-up. Methods: This descriptive, retrospective study used longitudinal data from German statutory health insurance claims. A model using coded data classified the patients with HF into ejection fraction (EF) categories. Individuals were selected during 2013, with an inclusion period from 2014 to 2015 and a follow-up from 2016 to 2020. Baseline characteristics included demographic data, disease stage, comorbidities, and risk factors. Follow-up criteria included major adverse cardiac events (MACEs), EF category, and mortality. Disease progression was visualized by Sankey plots. Results: Among the 173 195 individuals with T2D identified in 2013, 6725 (median age, 74 years) developed HF in 2014 or 2015. 34.4% of individuals had MACEs, and 42.9% died over 5 years. Myocardial infarction (42%) was the most common event, followed by stroke (32%) and hospitalization (28%). A total of 5282 (78.54%) patients were classified into preserved EF and 1443 (21.46%) into reduced EF. Survival after 5 years was 71% in HF for preserved EF patients, and 29% in the HF for those with reduced EF. Conclusion: Heart failure is relevant in individuals with diabetes. A high number of patients may likely not survive a 5-year period. Validation of the model with German data is highly desirable. New ways of close monitoring could help improve outcomes.

Pediatric Failure Rates and Speech Outcomes in the HiRes Ultra and Ultra 3D Series Recall.

The recent Field Corrective Action (FCA) for the HiRes Ultra and Ultra 3D (V1) cochlear implants (CIs) triggered much research investigating clinical identification, failure rates, and postrevision outcomes. Pediatric data remain limited, especially with regards to speech outcomes. We aim to characterize the trajectory of children implanted with these devices with specific attention to speech outcomes. Retrospective cohort study of pediatric patients with FCA-affected CIs from March 2017 to January 2020 at a tertiary children's hospital. CI placement, device monitoring, audiologic evaluation, revision surgery. CI failure rates, revision surgery rate, speech recognition outcomes. Forty-one devices were implanted in 27 pediatric patients. Average age at implantation was 4.01 years (range, 0.87-12.75). To date, 30 devices (73%) are known failures with 90% of these having undergone revision surgery. No statically significant difference was noted on open-set speech testing across best prerevision, immediate prerevision, and best postrevision time points. Best postrevision CNC scores had a mean score of 71% ± 26%, n = 16. Pediatric patients implanted with FCA-affected CI devices have a high risk of device failure. Open-set speech recognition was not significantly different from prerevision to postrevision testing, suggesting preserved speech outcomes. This may be partially attributable to limitations of cohort size and the pediatric population with open-set speech testing. However, we suspect that close follow-up with standardized testing and a low threshold for revision surgery provided by our multidisciplinary team may have mitigated these changes. Postrevision open-set speech testing remains positive for these patients.

The National Electrical Safety Code, powerline clearances, and wildfires

AbstractThe provisions of the National Electrical Safety Code (NESC) have a long, but undocumented history. They are the primary means by which Public Utilities Commission agencies in various States in the United States enforce requirements for electrical clearances pertinent to high‐voltage powerlines. Examination of the NESC provisions for clearances between grounded guy wires and distribution phase conductors in the context of the Woolsey Fire indicates a comprehensive lack of realism in the Code provisions. While they may be entirely sufficient to prevent sparkover under normal operating conditions, they are wholly insufficient to cope with even modest adverse events. The profession should consider explicitly assessing factors beyond sparkover that affect the adequacy of clearance requirements. The provisions of the NESC (and California's parallel General Order No. 95) should be systematically reexamined in order to ensure that safety regulations can cope with adverse events that are serious, but not extreme. Since the vast majority of the electrical power network is aging and not new construction, a scheme should be developed to establish priorities for upgrading existing facilities at the highest risk of failure.

Early therapeutic drug monitoring helps to identify inflammatory bowel disease patients with a high risk to fail thiopurine treatment.

Conventional thiopurines (azathioprine and mercaptopurine) remain standard therapy to maintain steroid sparing remission in inflammatory bowel disease (IBD), but are regularly discontinued due to adverse drug reactions (ADRs). Measurement of the metabolites 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine ribonucleotides (6-MMPR) and the 6-MMPR/6-TGN ratio, may predict the development of these ADRs. Our aim was to evaluate whether early thiopurine metabolite measurements were associated with clinical outcomes. A post-hoc analysis was conducted of a multicentre, prospective, observational study on thiopurine-induced hepatotoxicity. IBD patients who initiated thiopurine therapy were included and thiopurine metabolite concentrations were assessed after 7days (±1) (T1). Patients were monitored for 12 weeks to document the occurrence of ADRs, early treatment discontinuation and effectiveness. In total, 181 patients were evaluated. At T1, 6-MMPR concentrations and 6-TGN/6-MMPR ratios were independently related to treatment discontinuation within 12 weeks after correction for sex, age and body mass index (BMI) (P= .034 and .002, respectively). The largest effects were observed for 6-MMPR ≥3000pmol/8 × 108 RBC and 6-TGN/6-MMPR ratio ≥17. Furthermore, 6-MMPR concentrations and 6-TGN/6-MMPR ratios at T1 were independently related to skewed metabolism at steady state (Week 8, 6-MMPR/-6TGN ratio ≥11 and ≥20) (both P< .001). The occurrence of ADRs and effectiveness were not independently related to T1 thiopurine metabolite concentrations. Thiopurine metabolite concentrations at T1 were related to early treatment discontinuation and skewed metabolism at steady state, but not to effectiveness, helping to identify patients with a high risk of thiopurine treatment failure.

Weaning from mechanical ventilation during myasthenic crisis, a monocentric retrospective study

Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient’s age was 64 [42–76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3–10] days and the median total length of MV was 14 [10–23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials.