Role of allergen immunotherapy and biologics in allergic diseases.

The rise in the prevalence of allergic diseases has become a global health burden. Allergic diseases are a group of immune-mediated disorders characterized by IgE-mediated conditions resulting from a type 2 helper T cell (Th2)-skewed immune response. This review aims to comprehensively summarize recent research on the roles of allergen immunotherapy (AIT) and biologics in allergic diseases. Specifically, we review the mechanisms of AIT and biologics in modulating innate and adaptive immunity involved in allergic disease pathogenesis, as well as their safety and efficacy in the treatment of allergic diseases. We also discuss current new AIT strategies such as recombinant allergen-based vaccines and allergen extract nanoencapsulation. Further research is needed to understand immune tolerance mechanisms beyond the Th2 pathway and to characterize immunological changes in responders and nonresponders to AIT or biologics. This additional research may uncover new targets for monitoring treatment responses and developing personalized treatment strategies for allergic diseases.

Clinicopathological factors predicting pathological complete response to neoadjuvant anti-HER2 therapy in HER2-positive breast cancer.

Introduction Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown effectiveness against HER2-positive breast cancer. This makes neoadjuvant chemotherapy (NAC) a valuable option for treating both early and advanced stages of the disease. The tumor's response to HER2-targeted NAC provides crucial prognostic information. Additionally, it allows for tailoring adjuvant treatment strategies for HER2+ breast cancer based on pathological responses. This study aimed to investigate the clinicopathological factors that influence tumor response. Methods We retrospectively analyzed 122 patients diagnosed with HER2+ breast cancer. These patients received NAC and HER2-directed therapy between January 2018 and December 2022 at the Pusan National University Yangsan Hospital. Following surgery, tumor response was evaluated, categorizing patients into two groups: pathological complete response (pCR) and non-pCR groups. We analyzed data on various factors, including age, NAC regimen, type of breast and axillary surgery, clinical stage (cTNM), historical grade, and pre-operative levels of carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and KI-67. Results Out of the 122 patients, 75 achieved pCR, while 47 did not. Most clinicopathological factors showed no significant difference between the pCR and non-pCR groups. However, several factors were associated with a higher pCR rate: normal preoperative CA 15-3 levels (odds ratio [OR]: 3.74, confidence interval [CI]: 1.19-11.72, P = 0.02), preoperative-ER positivity (OR: 2.65, CI: 1.25-5.59, P = 0.01), PR negativity (OR: 3.92, CI: 1.82-8.45, P <0.05), and strong preoperative HER2 immunohistochemistry (IHC) 3+ staining. Multivariate analysis confirmed that PR negativity (OR: 2.8, CI: 1.23-6.42, P = 0.01) and strong preoperative-HER2 IHC 3+ staining (OR: 0.18, CI: 0.03-0.84, P = 0.04) were independent predictors of a higher pCR rate. Conclusions A pCR after NAC impacts patient prognosis and influences the choice of adjuvant treatment for HER2+ breast cancer. Clinicopathological factors can help predict responses to HER2-targeted NAC. In our study, pre-ER/PR negativity, high pre-HER2 levels, and normal CA 15-3 levels were found to be potential predictors of pCR. These findings may contribute to developing more effective treatment strategies for HER2+ breast cancer.

Three-Dimensional Morphological Analysis of the Suprascapular Notch in Patients with Arthroscopic Rotator Cuff Repair.

Background: The morphology of the suprascapular notch (SSN) and the ossification of the superior transverse suprascapular ligament (STSL) are risk factors for injury of the suprascapular nerve (SN) during arthroscopic shoulder procedures. The purpose of the current study was to compare preoperative clinical and radiologic characteristics between patients with and without STSL ossification and to evaluate SSN morphology in patients who underwent arthroscopic rotator cuff repair using a 3-dimensional (3D) reconstructed model. Methods: Patients who underwent arthroscopic rotator cuff repair and were given a computed tomography (CT) scan from March 2018 to August 2019 were included in this study. Patients were divided into 2 groups: those without STSL ossification (group I) and those with STSL ossification (group II). Tear size of the rotator cuff and fatty infiltration of rotator cuff muscles were assessed in preoperative magnetic resonance imaging. The morphology of the SSN was classified following Rengachary's classification. The transverse and vertical diameters of the SSN and the distances from anatomical landmarks to the STSL were measured. All measurements were completed using a 3D CT reconstructed scapula model. Results: A total of 200 patients were included in this study. One hundred seventy-eight patients (89.0%) without STSL ossification were included in group I, and 22 patients (11.0%) with STSL ossification were included in group II. Group II showed a significantly advanced age (61.0 ± 7.4 vs. 71.0 ± 7.3 years, p < 0.001) and a shorter transverse diameter of SSN (10.7 ± 3.1 mm vs. 6.1 ± 3.7 mm, p < 0.001) than group I. In the logistic regression analysis, age was an independent prognostic factor for STSL ossification (odds ratio, 1.201; 95% confidence interval, 1.112-1.296; p < 0.001). Patients in type VI showed significantly shorter transverse diameters than other types (p < 0.001). The patient with type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than those with other types (p < 0.001). Conclusions: In the 3D morphological analysis, age was the independent factor associated with STSL ossification in patients who underwent arthroscopic rotator cuff repair. Type VI showed significantly shorter transverse diameters than other types. Type I showed a significantly shorter distance from the articular surface of the glenoid to the SSN than other types.

Reorganization of H3K9me heterochromatin leads to neuronal impairment via the cascading destruction of the KDM3B-centered epigenomic network.

Histone H3K9 methylated heterochromatin silences repetitive non-coding sequences and lineage-specific genes during development, but how tissue-specific genes escape from heterochromatin in differentiated cells is unclear. Here, we examine age-dependent transcriptomic profiling of terminally differentiated mouse retina to identify epigenetic regulators involved in heterochromatin reorganization. The single-cell RNA sequencing analysis reveals a gradual downregulation of Kdm3b in cone photoreceptors during aging. Disruption of Kdm3b (Kdm3b +/- ) of 12-month-old mouse retina leads to the decreasing number of cones via apoptosis, and it changes the morphology of cone ribbon synapses. Integration of the transcriptome with epigenomic analysis in Kdm3b +/- retinas demonstrates gains of heterochromatin features in synapse assembly and vesicle transport genes that are downregulated via the accumulation of H3K9me1/2. Contrarily, losses of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that the KDM3B-centered epigenomic network is crucial for balancing of cone photoreceptor homeostasis via the modulation of gene set-specific heterochromatin features during aging.

PARCCS: A Machine Learning Risk-Prediction Model for Acute Peripartum Cardiovascular Complications During Delivery Admissions.

Background: Maternal mortality in the United States remains high, with cardiovascular (CV) complications being a leading cause. Objectives: The purpose of this paper was to develop the PARCCS (Prediction of Acute Risk for Cardiovascular Complications in the Peripartum Period Score) for acute CV complications during delivery. Methods: Data from the National Inpatient Sample (2016-2020) and International Classification of Diseases, Tenth Revision codes to identify delivery admissions were used. Acute CV/renal complications were defined as a composite of pre-eclampsia/eclampsia, peripartum cardiomyopathy, renal complications, venous thromboembolism, arrhythmias, and pulmonary edema. A risk prediction model, PARCCS, was developed using machine learning consisting of 14 variables and scored out of 100 points. Results: Of the 2,371,661 pregnant patients analyzed, 7.0% had acute CV complications during delivery hospitalization. Patients with CV complications had a higher prevalence of comorbidities and were more likely to be of Black race and lower income. The PARCCS variables included electrolyte imbalances (13 points [p]), age (3p for age <20 years), cesarean delivery (4p), obesity (5p), pre-existing heart failure (28p), multiple gestations (4p), Black race (2p), gestational hypertension (3p), low income (1p), gestational diabetes (2p), chronic diabetes (6p), prior stroke (22p), coagulopathy (5p), and nonelective admission (2p). Using the validation set, the performance of the model was evaluated with an area under the receiver-operating characteristic curve of 0.68 and a 95% CI of 0.67 to 0.68. Conclusions: PARCCS has the potential to be an important tool for identifying pregnant individuals at risk of acute peripartum CV complications at the time of delivery. Future studies should further validate this score and determine whether it can improve patient outcomes.

Doctor shopping trend of patients before undergoing rotator cuff repair in Korea: a multicenter study.

BACKGROUND: This study aims to investigate the trend of doctor shopping among patients with rotator cuff tear (RCT) before undergoing surgery and to examine the relevance of these findings to the public. METHODS: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. RESULTS: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000-5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with sex, age, VAS pain score immediately before surgery, or RCT size. CONCLUSIONS: Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment. Level of evidence: IV.

Biomechanical comparison between low profile 2.7 mm distal locking hook plate and 3.5 mm distal locking hook plate for acromioclavicular joint injury: A finite element analysis.

PURPOSE: Although hook plate fixation is popularly used, concerns exist regarding periprosthetic fractures and the necessity to remove the plate to prevent subacromial erosion and subsequent acromion fracture, due to its non-anatomical design. We hypothesized that a low profile 2.7 mm distal locking hook plate would provide comparable stability to a properly used 3.5 mm distal locking hook plate MATERIALS AND METHODS: A 3.5 mm distal locking plate (type 1) and a low profile 2.7 mm plate (type 2) were assessed by finite element analysis. Peak von Mises stress (PVMS) was calculated on the acromion's undersurface, clavicle shaft, and hook, focusing on how these stresses varied with the number and placement of distal locking screws. RESULTS: Increased distal screws in both types led to lower PVMS on the acromion's undersurface and the hook, with the lowest acromion PVMS observed in type 2 with three distal screws, and on the hook in type 1 with two distal screws. Increasing the number of distal screws similarly reduced PVMS on the clavicle shaft, with the lowest in type 1 with two distal screws. In both plate types, the most posterior distal locking screw played a crucial role in distributing stress across the acromion and the hook. CONCLUSION: The low profile 2.7 mm distal locking hook plate showed comparable biomechanical results to the 3.5 mm distal locking hook plate. Increasing the number of distal locking screws showed less stress concentration on the bone and hook in both models. The most posterior distal locking screw showed an essential role in stress distribution.

Improved differentiation of cavernous malformation and acute intraparenchymal hemorrhage on CT using an AI algorithm.

This study aimed to evaluate the utility of an artificial intelligence (AI) algorithm in differentiating between cerebral cavernous malformation (CCM) and acute intraparenchymal hemorrhage (AIH) on brain computed tomography (CT). A retrospective, multireader, randomized study was conducted to validate the performance of an AI algorithm in differentiating AIH from CCM on brain CT. CT images of CM and AIH (< 3 cm) were identified from the database. Six blinded reviewers, including two neuroradiologists, two radiology residents, and two emergency department physicians, evaluated CT images from 288 patients (CCM, n = 173; AIH, n = 115) with and without AI assistance, comparing diagnostic performance. Brain CT interpretation with AI assistance resulted in significantly higher diagnostic accuracy than without (86.92% vs. 79.86%, p < 0.001). Radiology residents and emergency department physicians showed significantly improved accuracy of CT interpretation with AI assistance than without (84.21% vs. 75.35%, 80.73% vs. 72.57%; respectively, p < 0.05). Neuroradiologists showed a trend of higher accuracy with AI assistance in the interpretation but lacked statistical significance (95.83% vs. 91.67%, p = 0.56). The use of an AI algorithm can enhance the differentiation of AIH from CCM in brain CT interpretation, particularly for nonexperts in neuroradiology.

CRACD loss induces neuroendocrine cell plasticity of lung adenocarcinoma.

Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, some lung adenocarcinoma (LUAD) cells transform into neuroendocrine (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD (capping protein inhibiting regulator of actin dynamics), a capping protein inhibitor, is frequently inactivated in cancers. CRACD knockout (KO) is sufficient to de-repress NE-related gene expression in the pulmonary epithelium and LUAD cells. In LUAD mouse models, Cracd KO increases intratumoral heterogeneity with NE gene expression. Single-cell transcriptomic analysis showed that Cracd KO-induced NE cell plasticity is associated with cell de-differentiation and stemness-related pathway activation. The single-cell transcriptomic analysis of LUAD patient tumors recapitulates that the distinct LUAD NE cell cluster expressing NE genes is co-enriched with impaired actin remodeling. This study reveals the crucial role of CRACD in restricting NE cell plasticity that induces cell de-differentiation of LUAD.

Age and sex-related differences in outcomes of OHCA patients after adjustment for sex-based in-hospital management disparities.

OBJECTIVES: Out-of-hospital cardiac arrest (OHCA) survival differences due to sex remain controversial. Previous studies adjusted for prehospital variables, but not sex-based in-hospital management disparities. We aimed to investigate age and sex-related differences in survival outcomes in OHCA patients after adjustment for sex-based in-hospital management disparities. METHODS: This retrospective observational study used a prospective multicenter OHCA registry to review data of patients from October 2015 to December 2020. The primary outcome was good neurological outcome defined as cerebral performance category score 1 or 2. We performed multivariable logistic regression and restricted cubic spline analysis according to age. RESULTS: Totally, 8988 patients were analyzed. Women showed poorer prehospital characteristics and received fewer coronary angiography, percutaneous coronary interventions, targeted temperature management, and extracorporeal membrane oxygenation than men. Good neurological outcomes were lower in women than in men (5.8% vs. 12.2%, p < 0.001). After adjustment for age, prehospital variables, and in-hospital management, women were more likely to have good neurological outcomes than men (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 1.07-1.74, p = 0.012). The restricted cubic spline curve showed a reverse sigmoid pattern of adjusted predicted probability of outcomes and dynamic associations of sex and age-based outcomes. CONCLUSIONS: Women with OHCA were more likely to have good neurological outcome after adjusting for age, prehospital variables, and sex-based in-hospital management disparities. There were non-linear associations between sex and survival outcomes according to age and age-related sex-based differences.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020].

Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

Structural insights into the octamerization of glycerol dehydrogenase.

Glycerol dehydrogenase (GDH) catalyzes glycerol oxidation to dihydroxyacetone in a NAD+-dependent manner. As an initiator of the oxidative pathway of glycerol metabolism, a variety of functional and structural studies of GDH have been conducted previously. Structural studies revealed intriguing features of GDH, like the flexible ß-hairpin and its significance. Another commonly reported structural feature is the enzyme's octameric oligomerization, though its structural details and functional significance remained unclear. Here, with a newly reported GDH structure, complexed with both NAD+ and glycerol, we analyzed the octamerization of GDH. Structural analyses revealed that octamerization reduces the structural dynamics of the N-domain, which contributes to more consistently maintaining a distance required for catalysis between the cofactor and substrate. This suggests that octamerization may play a key role in increasing the likelihood of the enzyme reaction by maintaining the ligands in an appropriate configuration for catalysis. These findings expand our understanding of the structure of GDH and its relation to the enzyme's activity.

Fracture Severity and Triangular Fibrocartilage Complex Injury in Distal Radius Fractures with or without Osteoporosis.

The purpose of this study was to investigate the fracture morphology of distal radius fractures (DRFs) with the status of triangular fibrocartilage complex (TFCC) foveal insertion in patients with or without osteoporosis and to identify the relationship between osteoporosis and foveal tear. Seventy-five patients who underwent surgery for DRF from January 2021 to September 2023 were included. All patients were evaluated by standard radiography and dual-energy X-ray absorptiometry and underwent a 3.0 T magnetic-resonance imaging examination of the involved wrist to identify TFCC foveal tear. Patients were allocated into two groups according to the presence of osteoporosis: patients with osteoporosis (group I) and those without osteoporosis (group II). Group I showed a significantly larger displacement of fractures compared to group II (radial inclination; 13.7 ± 5.4 vs. 17.9 ± 4.2; p < 0.001, dorsal angulation; 22.2 ± 12.1 vs. 16.5 ± 9.4; p = 0.024, ulnar variance; 4.15 ± 2.1 vs. 2.2 ± 1.9; p < 0.001). Dorsal angulation and ulnar variance were found to be independent prognostic factors for TFCC foveal tear in logistic regression analysis. Displacement of fractures was related to osteoporosis, and dorsal angulation and ulnar variance were independent prognostic factors for TFCC foveal tear. However, osteoporosis was not identified as a factor associated with TFCC foveal tears.

Is a Camera-Type Portable X-Ray Device Clinically Feasible in Chest Imaging?: Image Quality Comparison with Chest Radiographs Taken with Traditional Mobile Digital X-Ray Devices.

Purpose: To evaluate whether the image quality of chest radiographs obtained using a camera-type portable X-ray device is appropriate for clinical practice by comparing them with traditional mobile digital X-ray devices. Materials and Methods: Eighty-six patients who visited our emergency department and underwent endotracheal intubation, central venous catheterization, or nasogastric tube insertion were included in the study. Two radiologists scored images captured with traditional mobile devices before insertion and those captured with camera-type devices after insertion. Identification of the inserted instruments was evaluated on a 5-point scale, and the overall image quality was evaluated on a total of 20 points scale. Results: The identification score of the instruments was 4.67 ± 0.71. The overall image quality score was 19.70 ± 0.72 and 15.02 ± 3.31 (p < 0.001) for the mobile and camera-type devices, respectively. The scores of the camera-type device were significantly lower than those of the mobile device in terms of the detailed items of respiratory motion artifacts, trachea and bronchus, pulmonary vessels, posterior cardiac blood vessels, thoracic intervertebral disc space, subdiaphragmatic vessels, and diaphragm (p = 0.013 for the item of diaphragm, p < 0.001 for the other detailed items). Conclusion: Although caution is required for general diagnostic purposes as image quality degrades, a camera-type device can be used to evaluate the inserted instruments in chest radiographs.

3D Superclusters with Hybrid Bioinks for Early Detection in Breast Cancer.

The surface-enhanced Raman scattering (SERS) technique has garnered significant interest due to its ultrahigh sensitivity, making it suitable for addressing the growing demand for disease diagnosis. In addition to its sensitivity and uniformity, an ideal SERS platform should possess characteristics such as simplicity in manufacturing and low analyte consumption, enabling practical applications in complex diagnoses including cancer. Furthermore, the integration of machine learning algorithms with SERS can enhance the practical usability of sensing devices by effectively classifying the subtle vibrational fingerprints produced by molecules such as those found in human blood. In this study, we demonstrate an approach for early detection of breast cancer using a bottom-up strategy to construct a flexible and simple three-dimensional (3D) plasmonic cluster SERS platform integrated with a deep learning algorithm. With these advantages of the 3D plasmonic cluster, we demonstrate that the 3D plasmonic cluster (3D-PC) exhibits a significantly enhanced Raman intensity through detection limit down to 10-6 M (femtomole-(10-17 mol)) for p-nitrophenol (PNP) molecules. Afterward, the plasma of cancer subjects and healthy subjects was used to fabricate the bioink to build 3D-PC structures. The collected SERS successfully classified into two clusters of cancer subjects and healthy subjects with high accuracy of up to 93%. These results highlight the potential of the 3D plasmonic cluster SERS platform for early breast cancer detection and open promising avenues for future research in this field.

Bright diffusion sign: A sensitive and specific radiologic biomarker for multinodular and vacuolating neuronal tumor.

BACKGROUND AND PURPOSE: Accurate differentiation between multinodular and vacuolating neuronal tumor (MVNT) and dysembryoplastic neuroepithelial tumor (DNET) is important for treatment decision-making. We aimed to develop an accurate radiologic diagnostic model for differentiating MVNT from DNET using T2WI and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: A total of 56 patients (mean age, 47.48±17.78 years; 31 women) diagnosed with MVNT (n = 37) or DNET (n = 19) who underwent brain MRI, including T2WI and DWI, were included. Two board-certified neuroradiologists performed qualitative (bubble appearance, cortical involvement, bright diffusion sign, and bright apparent diffusion coefficient [ADC] sign) and quantitative (nDWI and nADC) assessments. A diagnostic tree model was developed with significant and reliable imaging findings using an exhaustive chi-squared Automatic Interaction Detector (CHAID) algorithm. RESULTS: In visual assessment, the imaging features that showed high diagnostic accuracy and interobserver reliability were the bright diffusion sign and absence of cortical involvement (bright diffusion sign: accuracy, 94.64 %; sensitivity, 91.89 %; specificity, 100.00 %; interobserver agreement, 1.00; absence of cortical involvement: accuracy, 92.86 %; sensitivity, 89.19 %; specificity, 100.00 %; interobserver agreement, 1.00). In quantitative analysis, nDWI was significantly higher in MVNT than in DENT (1.52 ± 0.34 vs. 0.91 ± 0.27, p < 0.001), but the interobserver agreement was fair (intraclass correlation coefficient = 0.321). The overall diagnostic accuracy of the tree model with visual assessment parameters was 98.21 % (55/56). CONCLUSION: The bright diffusion sign and absence of cortical involvement are accurate and reliable imaging findings for differentiating MVNT from DNET. By using simple, intuitive, and reliable imaging findings, such as the bright diffusion sign, MVNT can be accurately differentiated from DNET.

Oncologic outcome of breast reconstruction after mastectomy in breast cancer: a systematic review and meta-analysis.

Background: We conducted a comprehensive systematic review of the literature and meta-analysis of the oncologic outcomes of breast reconstruction (BR) after mastectomy and mastectomy only. This study aimed to analyze the impact of BR on the prognosis of patients with breast cancer. Methods: A systematic search of MEDLINE and EMBASE databases was performed using the following keywords: breast cancer, mastectomy, and BR. Inclusion criteria were studies reporting the survival data of patients after mastectomy only and mastectomy with BR. Event-free survival (EFS), breast cancer-specific survival (BCSS), and overall survival (OS) were considered the indicators of oncological outcomes. As all the included studies were non-randomized trials, we used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. The effect of BR on survival was measured using the effect size of the hazard ratio (HR). Data from each study were analyzed using the Review Manager. Results: Fifteen studies with 20,948 cases of BR and 63,358 cases of mastectomy were included. The pooled HRs for EFS and BCSS were 1.07 [95% confidence interval (CI): 0.78-1.47, P=0.65] and 0.84 (95% CI: 0.64-1.11, P=0.22), respectively. The patients who underwent BR after mastectomy had similar EFS and BCSS scores. Furthermore, patients who received BR had better OS (HR =0.73; 95% CI: 0.61-0.88, P=0.001) than those who underwent mastectomy only. Conclusions: The data showed that BR after mastectomy had similar EFS and BCSS and better OS than mastectomy alone. Our meta-analysis suggests that BR is a practicable and safe treatment option for patients with breast cancer.

Prediction of lactate concentrations after cardiac surgery using machine learning and deep learning approaches.

Background: Although conventional prediction models for surgical patients often ignore intraoperative time-series data, deep learning approaches are well-suited to incorporate time-varying and non-linear data with complex interactions. Blood lactate concentration is one important clinical marker that can reflect the adequacy of systemic perfusion during cardiac surgery. During cardiac surgery and cardiopulmonary bypass, minute-level data is available on key parameters that affect perfusion. The goal of this study was to use machine learning and deep learning approaches to predict maximum blood lactate concentrations after cardiac surgery. We hypothesized that models using minute-level intraoperative data as inputs would have the best predictive performance. Methods: Adults who underwent cardiac surgery with cardiopulmonary bypass were eligible. The primary outcome was maximum lactate concentration within 24 h postoperatively. We considered three classes of predictive models, using the performance metric of mean absolute error across testing folds: (1) static models using baseline preoperative variables, (2) augmentation of the static models with intraoperative statistics, and (3) a dynamic approach that integrates preoperative variables with intraoperative time series data. Results: 2,187 patients were included. For three models that only used baseline characteristics (linear regression, random forest, artificial neural network) to predict maximum postoperative lactate concentration, the prediction error ranged from a median of 2.52 mmol/L (IQR 2.46, 2.56) to 2.58 mmol/L (IQR 2.54, 2.60). The inclusion of intraoperative summary statistics (including intraoperative lactate concentration) improved model performance, with the prediction error ranging from a median of 2.09 mmol/L (IQR 2.04, 2.14) to 2.12 mmol/L (IQR 2.06, 2.16). For two modelling approaches (recurrent neural network, transformer) that can utilize intraoperative time-series data, the lowest prediction error was obtained with a range of median 1.96 mmol/L (IQR 1.87, 2.05) to 1.97 mmol/L (IQR 1.92, 2.05). Intraoperative lactate concentration was the most important predictive feature based on Shapley additive values. Anemia and weight were also important predictors, but there was heterogeneity in the importance of other features. Conclusion: Postoperative lactate concentrations can be predicted using baseline and intraoperative data with moderate accuracy. These results reflect the value of intraoperative data in the prediction of clinically relevant outcomes to guide perioperative management.

Culture conditions greatly impact the levels of vesicular and extravesicular Ago2 and RNA in extracellular vesicle preparations.

Extracellular vesicle (EV)-carried miRNAs can influence gene expression and functional phenotypes in recipient cells. Argonaute 2 (Ago2) is a key miRNA-binding protein that has been identified in EVs and could influence RNA silencing. However, Ago2 is in a non-vesicular form in serum and can be an EV contaminant. In addition, RNA-binding proteins (RBPs), including Ago2, and RNAs are often minor EV components whose sorting into EVs may be regulated by cell signaling state. To determine the conditions that influence detection of RBPs and RNAs in EVs, we evaluated the effect of growth factors, oncogene signaling, serum, and cell density on the vesicular and nonvesicular content of Ago2, other RBPs, and RNA in small EV (SEV) preparations. Media components affected both the intravesicular and extravesicular levels of RBPs and miRNAs in EVs, with serum contributing strongly to extravesicular miRNA contamination. Furthermore, isolation of EVs from hollow fiber bioreactors revealed complex preparations, with multiple EV-containing peaks and a large amount of extravesicular Ago2/RBPs. Finally, KRAS mutation impacts the detection of intra- and extra-vesicular Ago2. These data indicate that multiple cell culture conditions and cell states impact the presence of RBPs in EV preparations, some of which can be attributed to serum contamination.