Automated identification of thrombectomy amenable vessel occlusion on computed tomography angiography using deep learning.

Introduction: We developed and externally validated a fully automated algorithm using deep learning to detect large vessel occlusion (LVO) in computed tomography angiography (CTA). Method: A total of 2,045 patients with acute ischemic stroke who underwent CTA were included in the development of our model. We validated the algorithm using two separate external datasets: one with 64 patients (external 1) and another with 313 patients (external 2), with ischemic stroke. In the context of current clinical practice, thrombectomy amenable vessel occlusion (TAVO) was defined as an occlusion in the intracranial internal carotid artery (ICA), or in the M1 or M2 segment of the middle cerebral artery (MCA). We employed the U-Net for vessel segmentation on the maximum intensity projection images, followed by the application of the EfficientNetV2 to predict TAVO. The algorithm's diagnostic performance was evaluated by calculating the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: The mean age in the training and validation dataset was 68.7 ± 12.6; 56.3% of participants were men, and 18.0% had TAVO. The algorithm achieved AUC of 0.950 (95% CI, 0.915-0.971) in the internal test. For the external datasets 1 and 2, the AUCs were 0.970 (0.897-0.997) and 0.971 (0.924-0.990), respectively. With a fixed sensitivity of 0.900, the specificities and PPVs for the internal test, external test 1, and external test 2 were 0.891, 0.796, and 0.930, and 0.665, 0.583, and 0.667, respectively. The algorithm demonstrated a sensitivity and specificity of approximately 0.95 in both internal and external datasets, specifically for cases involving intracranial ICA or M1-MCA occlusion. However, the diagnostic performance was somewhat reduced for isolated M2-MCA occlusion; the AUC for the internal and combined external datasets were 0.903 (0.812-0.944) and 0.916 (0.816-0.963), respectively. Conclusion: We developed and externally validated a fully automated algorithm that identifies TAVO. Further research is needed to evaluate its effectiveness in real-world clinical settings. This validated algorithm has the potential to assist early-career physicians, thereby streamlining the treatment process for patients who can benefit from endovascular treatment.

A hybrid approach to improvement of watershed water quality modeling by coupling process-based and deep learning models.

Watershed water quality modeling to predict changing water quality is an essential tool for devising effective management strategies within watersheds. Process-based models (PBMs) are typically used to simulate water quality modeling. In watershed modeling utilizing PBMs, it is crucial to effectively reflect the actual watershed conditions by appropriately setting the model parameters. However, parameter calibration and validation are time-consuming processes with inherent uncertainties. Addressing these challenges, this research aims to address various challenges encountered in the calibration and validation processes of PBMs. To achieve this, the development of a hybrid model, combining uncalibrated PBMs with data-driven models (DDMs) such as deep learning algorithms is proposed. This hybrid model is intended to enhance watershed modeling by integrating the strengths of both PBMs and DDMs. The hybrid model is constructed by coupling an uncalibrated Soil and Water Assessment Tool (SWAT) with a Long Short-Term Memory (LSTM). SWAT, a representative PBM, is constructed using geographical information and 5-year observed data from the Yeongsan River Watershed. The output variables of the uncalibrated SWAT, such as streamflow, suspended solids (SS), total nitrogen (TN), and total phosphorus (TP), as well as observed precipitation for the day and previous day, are used as training data for the deep learning model to predict the TP load. For the comparison, the conventional SWAT model is calibrated and validated to predict the TP load. The results revealed that TP load simulated by the hybrid model predicted the observed TP better than that predicted by the calibrated SWAT model. Also, the hybrid model reflects seasonal variations in the TP load, including peak events. Remarkably, when applied to other sub-basins without specific training, the hybrid model consistently outperformed the calibrated SWAT model. In conclusion, application of the SWAT-LSTM hybrid model could be a useful tool for decreasing uncertainties in model calibration and improving the overall predictive performance in watershed modeling. PRACTITIONER POINTS: We aimed to enhance process-based models for watershed water-quality modeling. The Soil and Water Assessment Tool-Long Short-Term Memory hybrid model's predicted and total phosphorus (TP) matched the observed TP. It exhibited superior predictive performance when applied to other sub-basins. The hybrid model will overcome the constraints of conventional modeling. It will also enable more effective and efficient modeling.

Applying interpretable machine learning in computational biology-pitfalls, recommendations and opportunities for new developments.

Recent advances in machine learning have enabled the development of next-generation predictive models for complex computational biology problems, thereby spurring the use of interpretable machine learning (IML) to unveil biological insights. However, guidelines for using IML in computational biology are generally underdeveloped. We provide an overview of IML methods and evaluation techniques and discuss common pitfalls encountered when applying IML methods to computational biology problems. We also highlight open questions, especially in the era of large language models, and call for collaboration between IML and computational biology researchers.

Risk prediction of multiple-station N2 metastasis in patients with upfront surgery for clinical single-station N2 non-small cell lung cancer.

To investigate long-term outcomes and develop a risk model for pathological multi-station N2 (pN2b) in patients who underwent upfront surgery for clinical single-station N2 (cN2a) non-small cell lung cancer (NSCLC). From 2006 to 2018, 547 patients who had upfront surgery for suspected cN2a NSCLC underwent analysis. A risk model for predicting pN2b metastasis was developed using preoperative clinical variables via multivariable logistic analysis. Among 547 clinical cN2a NSCLC patients, 118 (21.6%), 58 (10.6%), and 371 (67.8%) had pN0, pN1, and pN2. Among 371 pN2 NSCLC patients, 77 (20.8%), 165 (44.5%), and 129 (34.7%) had pN2a1, pN2a2, and pN2b. The 5-year overall survival rates for pN2a1 and pN2a2 were significantly higher than for pN2b (p = 0.041). Histologic type (p < 0.001), age ≤ 50 years (p < 0.001), preoperatively confirmed N2 metastasis (p < 0.001), and clinical stage IIIB (vs. IIIA) (p = 0.003) were independent risk factors for pN2b metastasis. The risk scoring system based on this model demonstrated good discriminant ability for pN2b disease (area under receiver operating characteristic: 0.779). In cN2a NSCLC patients, those with multiple N2 metastases indicate worse prognosis than those with a single N2 metastasis. Our risk scoring system effectively predicts pN2b in these patients.

Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

Single point insulin sensitivity estimator index for identifying metabolic syndrome in US adults: NHANES 2017-march 2020.

PURPOSE: Single Point Insulin Sensitivity Estimator (SPISE) index was recently introduced as a reliable indirect indicator of insulin resistance, applicable to large population-based research. Here, we aimed to 1) examine racial/ethnic differences in SPISE index among US adults, 2) compare predictive power of SPISE index for metabolic syndrome (MetSyn) by race/ethnicity, and 3) evaluate its predictive power for MetSyn against other well-known IR indices including Triglyceride/HDL-C, Triglyceride-glucose index, homeostatic model assessment for insulin resistance, and inverse fasting insulin. METHODS: A total of 2168 adults (814 white, 690 black, and 664 Hispanic) from NHANES 2017-March 2020 Pre-Pandemic Data was analyzed in this study. MetSyn was defined by the AHA/NHLBI criteria. SPISE index and insulin resistance indices were calculated by using physical and cardiometabolic parameters. RESULTS: SPISE index was lowest in Hispanic, followed by black and white, with no difference between white vs. black. The area under the curve of receiver operating characteristics of SPISE index for predicting MetSyn was highest in white (88 %), followed by Hispanic (86 %) and black (82 %) (P < 0.05 vs. black), with optimal cutoffs of 5.03, 4.84, and 4.89, respectively. In the total cohort, the predictive power of the SPISE index for MetSyn was 85 %, higher than the other insulin resistance indices (all P < 0.05). CONCLUSIONS: SPISE index outperforms various insulin resistance indices for predicting MetSyn in US adults, signifying its potential in large-scale observational studies. Race/ethnicity should be stratified when using the SPISE index as its predictive power and cutoffs for predicting MetSyn vary by race/ethnicity.

Clinical and radiographic outcomes after mechanical thrombectomy in medium-vessel posterior cerebral artery occlusions: Subgroup analysis from STAR.

BACKGROUND: Whereas mechanical thrombectomy (MT) has become standard-of-care treatment for patients with salvageable brain tissue after acute stroke caused by large-vessel occlusions, the results of MT in patients with medium-vessel occlusions (MEVOs), particularly in the posterior cerebral artery (PCA), are not well known. METHODS: Using data from the international Stroke Thrombectomy and Aneurysm Registry (STAR), we assessed presenting characteristics and clinical outcomes for patients who underwent MT for primary occlusions in the P2 PCA segment. As a subanalysis, we compared the PCA MeVO outcomes with STAR's anterior circulation MeVO outcomes, namely middle cerebral artery (MCA) M2 and M3 segments. RESULTS: Of the 9812 patients in STAR, 43 underwent MT for isolated PCA MeVOs. The patients' median age was 69 years (interquartile range 61-79), and 48.8% were female. The median NIH Stroke Scale score was 9 (range 6-17). After recanalization, 67.4% of patients achieved successful recanalization (modified treatment in cerebral infarction score [mTICI] ≥ 2b), with a first-pass success rate of 44.2%, and 39.6% achieved a modified Rankin score of 0-2 at 90 days. Nine patients (20.9%) had died by the 90-day follow-up. In comparison with M2 and M3 MeVOs, there were no differences in presenting characteristics among the three groups. Patients with PCA MeVOs were less likely to undergo intra-arterial thrombolysis (4.7% PCA vs. 10.1% M2 vs. 16.2% M3, p = 0.046) or to achieve successful recanalization (mTICI ≥ 2b, 67.4%, 86.7%, 82.3%, respectively, p < 0.001); however, there were no differences in the rates of successful first-pass recanalization (44.2%, 49.8%, 52.3%, respectively, p = 0.65). CONCLUSIONS: We describe the STAR experience performing MT in patients with PCA MeVOs. Our analysis supports that successful first-pass recanalization can be achieved in PCA MEVOs at a rate similar to that in MCA MeVOs, although further study and possible innovation may be necessary to improve successful PCA MeVO recanalization rates.

Spatial profiling of non-small cell lung cancer provides insights into tumorigenesis and immunotherapy response.

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment. Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI). In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment. In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated. Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity. Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue. Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis. These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients.

Infective endocarditis.

First described more than 350 years ago, infective endocarditis represents a global health concern characterised by infections affecting the native or prosthetic heart valves, the mural endocardium, a septal defect, or an indwelling cardiac device. Over recent decades, shifts in causation and epidemiology have been observed. Echocardiography remains pivotal in the diagnosis of infective endocarditis, with alternative imaging modalities gaining significance. Multidisciplinary management requiring expertise of cardiologists, cardiovascular surgeons, infectious disease specialists, microbiologists, radiologists and neurologists, is imperative. Current recommendations for clinical management often rely on observational studies, given the limited number of well conducted randomised controlled trials studying infective endocarditis due to the rarity of the disease. In this Seminar, we provide a comprehensive overview of optimal clinical practices in infective endocarditis, highlighting key aspects of pathophysiology, pathogens, diagnosis, management, prevention, and multidisciplinary approaches, providing updates on recent research findings and addressing remaining controversies in diagnostic accuracy, prevention strategies, and optimal treatment.

Phase 3 Study Assessing Lot-to-lot Consistency of RSVPreF3 Vaccine and its Immune Response, Safety, and Reactogenicity When Co-administered with FLU-D-QIV.

BACKGROUND: A single-dose investigational respiratory syncytial virus (RSV) vaccine, RSV prefusion protein F3 (RSVPreF3), was co-administered with a single-dose quadrivalent influenza vaccine (FLU-D-QIV) in a phase 3, randomized, controlled, multicenter study in healthy, non-pregnant women aged 18-49 years. METHODS: The study was observer-blind to evaluate the lot-to-lot consistency of RSVPreF3, and single-blind to evaluate the immune response, safety, and reactogenicity of RSVPreF3 co-administered with FLU-D-QIV. RESULTS: A total of 1415 participants were included in the per-protocol set. There was a robust immune response at day 31 across each of the 3 RSVPreF3 vaccine lots; adjusted geometric mean concentration ratios (95% confidence interval [CI]) were 1.01 (0.91, 1.12), 0.93 (0.84, 1.03), and 0.92 (0.83, 1.02) for RSV1/RSV2, RSV1/RSV3, and RSV2/RSV3, respectively. For FLU-D-QIV co-administered with RSVPreF3, versus FLU-D-QIV alone at day 31, noninferiority was satisfied for 3 of 4 strains assessed, with the lower limit of the 95% CI for geometric mean ratio >0.67. CONCLUSIONS: Immunogenic consistency was demonstrated for 3 separate lots of RSVPreF3. Immunogenic noninferiority was demonstrated when comparing FLU-D-QIV administered alone, versus co-administered with RSVPreF3, for 3 strains of FLU-D-QIV. Co-administration was well tolerated, and both vaccines had clinically acceptable safety and reactogenicity profiles. CLINICAL TRIALS REGISTRATION: NCT05045144; EudraCT, 2021-000357-26.

This was a phase 3 study that compared antibodies against respiratory syncytial virus (or RSV for short) between women who were given 3 different production batches of RSV prefusion protein F3 (known as RSVPreF3) vaccine. The study also compared the antibodies between women who received either an RSV vaccine together with a flu vaccine (known as FLU-D-QIV), or a flu vaccine alone. The flu vaccine contained 4 different strains of flu virus. The study involved 1415 healthy, non-pregnant women aged 18­49 years. The antibodies checked after 31 days showed strong immune responses for all 3 RSV vaccine production batches, and similar immune responses between each of the 3 RSV vaccine production batches. The immune response of 3 of the 4 flu strains was not less when the flu vaccine was given together with the RSV vaccine than the immune response when flu vaccine was given alone and both vaccines were well tolerated.

Does a Point-of-Care 3-Dimensional Printer Result in a Decreased Length of Surgery for Orbital Fractures?

BACKGROUND: Utilization of point-of-care 3-dimensional printing (3DP) has decreased length of surgery in facial trauma. Little is known regarding 3DP's impact on length of surgery in orbital fracture. PURPOSE: The purpose of this study was to compare length of surgery between 3DP/preadapted (3DPPA) orbital plates and intraoperative adapted plates (IOAP) for orbital fracture reconstruction. STUDY DESIGN, SETTING, SAMPLE: This was a prospective, non-blinded, randomized clinical study of consecutive subjects with orbital fractures presented to Grady Memorial Hospital in Atlanta, Georgia, between January 2018 and June 2021. Subjects ≥ 18 years, unilateral fracture, no previous orbital surgery, and/or congenital craniofacial anomaly were included. We excluded subjects <18 years and bilateral fractures. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: Primary predictor variable was the treatment approach. Randomization software was used, and subjects were randomized to 3DPPA or IOAP groups. MAIN OUTCOME VARIABLE(S): Primary outcome variable was length of surgery in minutes. Secondary outcomes were the time required for plate insertion and fixation in minutes, operating room (OR) charges, and orbital volume (OV) calculation. COVARIATES: Age, sex, race, etiology, laterality, location, dimension, indication for surgery, postoperative enophthalmos, and diplopia. ANALYSES: Univariate and bivariate analyses were calculated. Statistical significance was P < .05. RESULTS: Twenty-five subjects met the inclusion criteria. Mean ages in 3DPPA and conventional IOAP groups were 41.5 (±9) and 38.2 (±10, P = .31), respectively. The mean length of surgery was 32.6 (±13.7) in 3DPPA and 53.3 (±12.8, P < .001) in conventional IOAP. The mean time required for plate insertion and fixation was 15.8n (±14.4) in 3DPPA and 41.4 (±9.4, P < .001) in conventional IOAP. The mean OR charges were $1,072.5 (±524.6) in 3DPPA and $1,757.3 (±422.6, P ≤ 0.001) in conventional IOAP. The mean calculated OV of uninjured and reconstructed orbit for the 3DPPA was 23.5 (±3.2)cm3 and 23 (±3.5, P = .37)cm3, respectively. The mean calculated OV of uninjured and reconstructed orbit for conventional IOAP was 28.6 (±3.6)cm3 and 22.8 (±2.6, P < .001)cm3, respectively. CONCLUSION AND RELEVANCE: Using 3DP to produce a model that enables preoperative plate bending/adaptation reduces the length of surgery, decreases OR charges, and results in predictable OV.

Mitral valve repair with leaflet resection versus preservation for degenerative posterior leaflet prolapse.

OBJECTIVES: The optimal technique for repairing posterior mitral valve leaflet prolapse remains undetermined. We aimed to compare leaflet resection and neochordae implantation in patients undergoing mitral valve repair for posterior leaflet prolapse, focusing on transmitral pressure gradient and recurrence of mitral regurgitation. METHODS: We enrolled patients undergoing mitral valve repair using either leaflet resection or neochordae implantation for single-segment prolapse of posterior mitral valve leaflet between 2000 and 2021 at our institution. Longitudinal outcomes were evaluated after adjustments with inverse-probability-of-treatment weighting. Repeat echocardiographic measurements (n = 3473, 5.4/patient) of transmitral pressure gradient and significant (moderate or severe) mitral regurgitation recurrence were estimated using nonlinear mixed-effect models. Subgroup analyses were conducted based on the size and type of prosthesis. RESULTS: Among 639 patients, leaflet resection was used in 479 (75.0%) and neochordae implantation was used in 160 (25.0%). In the inverse-probability-of-treatment weighting adjusted cohort, the risk of death (P = .623) and mitral valve reoperation (P = .340) did not significantly differ between the 2 groups during a median follow-up of 97.3 months. Echocardiographic data showed comparable mean (at 5 years, 3.8 vs 4.0 mm Hg; P = .442) and peak (9.6 vs 10.4 mm Hg; P = .131) pressure gradients between groups, which persisted in most subgroup analyses. However, neochordae implantation was associated with a higher probability of significant mitral regurgitation recurrence compared with leaflet resection (at 5 years, 16.1% vs 7.0%; P < .001). CONCLUSIONS: Leaflet resection yielded similar clinical outcomes and transmitral pressure gradients compared with neochordae implantation after mitral valve repair, with a lower mitral regurgitation recurrence rate. These findings underscore the need to reassess the efficacy of neochordae implantation relative to leaflet resection.

Isolated Acute Dysphagia as a Probable Rare Presentation of Guillain-Barré Syndrome with Complete Recovery: A Case Report.

Dysphagia is prevalent among the elderly and can lead to serious complications, often manifesting as a clinical symptom of various neurological or muscular pathologies, including Guillain-Barré Syndrome (GBS). GBS is an acute immune-mediated polyradiculoneuropathy, and dysphagia may arise during its course due to cranial nerve involvement. In rare GBS variants, dysphagia may present as the initial or sole clinical manifestation, posing diagnostic challenges. In this study, we present the case of an elderly female patient with dysphagia, eventually diagnosed with an atypical variant of GBS. Initially, the patient required nasogastric tube feeding; however, complete recovery was achieved through immunotherapy. This case underscores the importance of clinicians conducting thorough evaluations of factors influencing the swallowing mechanism and remaining vigilant about identifying uncommon causative factors. Such approaches enable the implementation of effective disease-modifying therapies, potentially leading to the resolution of dysphagic symptoms.

Luminescent Cs8PbBr64+ Quantum Dots Centered on the Octahedral PbBr64- Cluster within Zeolite LTA: Exploring the Edge of Three-Dimensional Crystal Structure and Its Stability.

The perovskite quantum dots (QDs) of CsPbX3 (X = Cl, Br, I) exhibit exceptional photoluminescent properties, but their sensitivity to moisture and heat poses a challenge. This study presents a solvent-free synthesis approach for incorporating CsPbBr3 perovskite QDs into zeolite A. The introduction of [Cs8PbBr6]4+ perovskite QDs into the zeolite framework resulted in a highly stable configuration, maintaining its initial luminescence properties even after being underwater or exposed to heat. The structure is determined by 3-dimensional single-crystal crystallography. Each octahedral PbBr64- ion is surrounded by Cs+ ions and [Cs8PbBr6]4+ perovskite QDs being formed at the 32% of the center of a large cavity. Further, [Na12CsBr8]5+ QDs are formed at the very center of another 46% large cavities by combining Cs+, Na+, and Br- ions. The peak in the emission spectrum of Pb,Br,Cs,Na-A is similar to those of the CsPbBr3 nanocrystal, Cs4PbBr6 0-dimensional perovskite QDs, and Pb,Br,H,Cs,Na-FAU(X and Y). This work demonstrates that Pb,Br,Cs,Na-A can be produced using a simplified solvent-free synthesis procedure, which exhibits excellent stability against moisture and heat. Moreover, through a straightforward process, various quantum dots (QDs) can be incorporated into zeolite cavities to develop materials with variety photoluminescent properties.

Endotype and Phenotype Related Postoperative Effects of Bacterial Lysate in Chronic Rhinosinusitis.

OBJECTIVES: Chronic rhinosinusitis (CRS) endotypes have demonstrated clinical value in guiding treatment decisions. Bacterial lysates are immunomodulators that have shown beneficial effects in various respiratory inflammatory diseases. This study aimed to evaluate the effect of postoperative bacterial lysate therapy on different CRS endotypes. METHODS: Patients diagnosed with CRS who underwent endoscopic sinus surgery were recruited. Bacterial lysates were administered postoperatively for 10 days per month for 3 months to the experimental group comprising patients with a history of frequent upper respiratory infections without adverse reactions. The remaining participants were allocated to the control group. The results of the postoperative 3-, 6-, and 12-month assessments, including the modified Lund-Kennedy (mLK) endoscopic and Sinonasal Outcome Test (SNOT) 22 scores, for the groups were compared. The tissue samples obtained from the participants were evaluated to detect the presence of relevant inflammatory mediators. RESULTS: Among the 92 participants, 47 started bacterial lysate therapy 2 weeks after the surgery. The tissue cytokine profiles and clinical parameters, such as the disease severity and blood eosinophil percentage, of the bacterial lysate and control groups were comparable before treatment. The mLK endoscopic and SNOT-22 scores did not differ after 3, 6, and 12 months of follow-up. The subgroup analysis revealed that the bacterial lysate group had significantly lower mLK endoscopic scores than the control group for CRS without nasal polyps, while there was a tendency toward significance for the interleukin (IL)-5 negative group after 6 months. CONCLUSION: Postoperative bacterial lysate therapy has some beneficial effects on the endoscopic findings of patients with CRS without nasal polyps or those who are negative for IL-5.

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells.

Primary cilia are crucial for cellular balance, serving as sensors for external conditions. Nephronophthisis and related ciliopathies, which are hereditary and degenerative, stem from genetic mutations in cilia-related genes. However, the precise mechanisms of these conditions are still not fully understood. Our research demonstrates that downregulating PDIA6, leading to cilia removal, makes cells more sensitive to ferroptotic death caused by endoplasmic reticulum (ER) stress. The reduction of PDIA6 intensifies the ER stress response, while also impairing the regulation of primary cilia in various cell types. PDIA6 loss worsens ER stress, hastening ferroptotic death in proximal tubule epithelial cells, HK2 cells. Counteracting this ER stress can mitigate PDIA6 depletion effects, restoring both the number and length of cilia. Moreover, preventing ferroptosis corrects the disrupted primary ciliogenesis due to PDIA6 depletion in HK2 cells. Our findings emphasize the role of PDIA6 in primary ciliogenesis, and suggest its absence enhances ER stress and ferroptosis. These insights offer new therapeutic avenues for treating nephronophthisis and similar ciliopathies.

Automated segmentation of MRI white matter hyperintensities in 8,421 patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To date, only a few small studies have attempted deep learning-based automatic segmentation of white matter hyperintensity (WMH) lesions in patients with cerebral infarction, which is complicated because stroke-related lesions can obscure WMH borders. We developed and validated deep learning algorithms to segment WMH lesions accurately in patients with cerebral infarction, using multisite datasets involving 8,421 patients with acute ischemic stroke. MATERIALS AND METHODS: We included 8,421 stroke patients from 9 centers in Korea. 2D UNet and SE-Unet models were trained using 2,408 FLAIR MRI from 3 hospitals and validated using 6,013 FLAIR MRIs from 6 hospitals. WMH segmentation performance was assessed by calculating DSC, correlation coefficient, and concordance correlation coefficient compared to a human-segmented gold standard. In addition, we obtained an uncertainty index that represents overall ambiguity in the voxel classification for WMH segmentation in each patient based on the Kullback-Leibler divergence. RESULTS: In the training dataset, the mean age was 67.4±13.0 years and 60.4% were men. The mean (95% CI) DSCs for Unet in internal testing and external validation were respectively 0.659 (0.649-0.669) and 0.710 (0.707-0.714), which were slightly lower than the reliability between humans (DSC=0.744; 95% CI=0.738-0.751; P=.031). Compared with the Unet, the SE-Unet demonstrated better performance, achieving a mean DSC of 0.675 (0.666-0.685; P<.001) in the internal testing and 0.722 (0.719-0.726; P<.001) in the external validation; moreover, it achieved high DSC values (ranging from 0.672 to 0.744) across multiple validation datasets. We observed a significant correlation between WMH volumes that were segmented automatically and manually for the Unet (r=0.917, P<.0001) and even stronger for the SE-Unet (r=0.933, P<.0001). The SE-Unet also attained a high concordance correlation coefficient (ranging from 0.841 to 0.956) in external test datasets. In addition, the uncertainty indices in the majority of patients (86%) in the external datasets were below 0.35, with an average DSC of 0.744 in these patients. CONCLUSIONS: We developed and validated deep learning algorithms to segment WMH in patients with acute cerebral infarction using the largest-ever MRI datasets. In addition, we showed that the uncertainty index can be used to identify cases where automatic WMH segmentation is less accurate and requires human review. ABBREVIATIONS: WMH = white matter hyperintensity; CNN = convolutional neural networks; SE = squeeze-and-excitation; KL = Kullback-Leibler; ReLU = rectified linear unit; LKW = last known well; mRS = modified Rankin Scale; NIHSS = National Institute of Health Stroke Scale; LAA = large artery atherosclerosis; SVO = small vessel occlusion; CE = cardioembolism.

Drugs Effective for Nonsteroidal Anti-inflammatory Drugs or Aspirin-induced Small Bowel Injuries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: The frequency of small bowel (SB) injuries has increased due to the increased use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. This study was a systematic review and meta-analysis to compare drugs effective for SB injuries caused by NSAIDs or aspirin use. METHODS: We searched MEDLINE, Embase, and Cochrane registries for randomized controlled trials through February 2023. The extracted data included changes in the number of erosions or ulcers in the jejunum or ileum observed through capsule endoscopy in patients taking NSAIDs or aspirin and administration of various mucoprotectants. We investigated the therapeutic or preventive efficacy of these drugs. The methodological bias was evaluated using Risk of Bias 2.0. RESULTS: Eighteen randomized controlled trials of drugs effective for NSAIDs or aspirin-induced SB injuries were included and analyzed. The agents used to treat or prevent SB injuries were rebamipide, misoprostol, geranylgeranylacetone, and probiotics. In the meta-analysis, the mucoprotectants that showed a significant effect in treating NSAID users, who developed SB injuries, were misoprostol (mean difference: -9.88; 95% CI: -13.26 to -6.50). Meanwhile, the mucoprotectant that can prevent SB injuries caused by NSAIDs or aspirin in the general population was rebamipide (mean difference: -1.85; 95% CI: -2.74 to -0.96). CONCLUSIONS: Misoprostol was effective in treating SB injuries caused by NSAIDs or aspirin (CRD42023410946).

Outcomes and differences by occluded vessel after endovascular thrombectomy for isolated medium vessel occlusions.

BACKGROUND: The outcomes of endovascular thrombectomy (EVT) for medium vessel occlusions (MeVOs) of specific vascular territories remain unknown. We aimed to investigate EVT outcomes by MeVO locations using the data from an ongoing international multicenter registry. METHODS: Patients with isolated MeVO who underwent EVT between January 2013 and December 2022 were retrospectively analyzed. Isolated MeVO was defined as an occlusion of the A2 or A3 (A2/A3), M2 or M3, and P2 or P3 (P2/P3). Outcomes included a 90-day modified Rankin score (mRS) of 0-2, successful recanalization (modified Thrombolysis in Cerebral Infarction score ≥ 2b), early neurological deterioration (END) or improvement (ENI), and 90-day mortality. END was defined as a worsening of ≥4 points from the baseline National Institutes of Health Stroke Scale (NIHSS) score within 24 h of EVT, while ENI was defined as an improvement of ≥4 points from the baseline NIHSS score within 24 h of EVT. RESULTS: 1744 MeVOs included. Compared to M2 occlusions (n = 1542, 88.4%), A2/A3 (n = 36, 2.1%) occlusions had lower odds of 90-day mRS 0-2 (adjusted odds ratio [aOR] 0.30, 95% confidence interval [CI] 0.11-0.80), and P2/P3 occlusions (n = 49, 2.8%) had lower odds of successful recanalization (aOR 0.19, 95% CI 0.07-0.50), and higher odds of END (aOR 3.53, 95% CI 1.35-9.25). Other outcomes showed no significant differences. CONCLUSIONS: A2/A3 occlusions were more likely to have worse outcomes compared to M2 occlusions after EVT for patients with isolated MeVOs.