A spectral bias-error stepwise correction method of plasma image-spectrum fusion based on deep learning for improving the performance of LIBS.

Poor spectral stability seriously hinders the wide application of laser-induced breakdown spectroscopy (LIBS), so how to improve its stability is the focus, hotspot, and difficulty of current research. In this study, to achieve high precision quantitative analysis under complex detection conditions, utilizing the fusion of multi-dimensional plasma information and the integration of physical models and algorithmic models, a spectral bias-error stepwise correction method of plasma image-spectrum fusion based on deep learning (SBESC-PISF) was proposed. In this method, based on the statistical properties of LIBS spectra, the actual obtained spectra were decomposed into three parts: the ideal spectral intensity related only to the element concentration, and the spectral bias and spectral error caused by the fluctuation of complex high-dimensional plasma parameters. Further, the deep learning methods were used to fully excavate all the effective features in the plasma images and spectra to invert the complex high-dimensional plasma parameters according to the physical models. Finally, the estimation models of spectral bias and spectral error were established based on these features, to realize the high-precision correction of spectral intensity. To verify the feasibility of SBESC-PISF, the spectra of aluminum alloy samples obtained under three complex detection conditions were used for analysis. Under the experimental condition of laser energy fluctuation, after correction by SBESC-PISF, R2 of the three calibration curves was all increased to 0.999, RMSE and STD of the validation set (RMSEV, STDV) were reduced by 55.246 % and 50.167 %, respectively. Under the experimental condition of defocusing amount fluctuation, R2 was also all increased to 0.999, RMSEV and STDV were decreased by 58.201 % and 51.006 %, respectively. When the laser energy and defocusing amount fluctuate simultaneously, R2 was increased to 0.999, 0.996 and 0.988, RMSEV and STDV were reduced by 58.776 % and 54.397 %, respectively. These experimental results demonstrate that the spectral fluctuation correction of SBESC-PISF under complex detection conditions is effective and has wide applicability.

Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

Changes in portal pulsatility index induced by a fluid challenge in patients with haemodynamic instability and systemic venous congestion: a prospective cohort study.

BACKGROUND: It is uncertain whether fluid administration can improve patients with systemic venous congestion and haemodynamic instability. This study aimed to describe the changes in systemic venous congestion and peripheral perfusion parameters induced by a fluid challenge in these patients, and to analyse the influence of the fluid responsiveness status on these changes. METHODS: The study is a single-centre prospective cohort study of 36 critically ill ICU patients with haemodynamic instability and a maximum vena cava diameter ≥ 20 mm. Changes in cardiac index during a fluid challenge (4 mL/kg of lactated Ringer's solution during 5 min) assessed by pulse contour analysis, central venous pressure, ultrasound systemic congestion parameters (portal venous flow pulsatility index, supra hepatic and intrarenal venous Doppler), and peripheral perfusion parameters (capillary refill time and peripheral perfusion index) were assessed in the overall population. All these data were compared between patients presenting a cardiac index increase > 10% during the fluid challenge (fluid responders) and the others (fluid non-responders). RESULTS: Twenty-eight (78%) patients were admitted for postoperative care following cardiac surgery; their mean ± SD left ventricular ejection fraction was 42 ± 9% and right ventricular dysfunction was found in at least 61% of the patients. The mean ± SD SOFA score was 9 ± 3. Thirteen (36%) patients were fluid responders. The fluid challenge administration induced a significant increase in portal pulsatility index, VExUS score, and central venous pressure without significant difference of these changes between fluid responders and non-responders. No significant change in perfusion parameters was observed. CONCLUSION: Fluid administration in patients with haemodynamic instability and systemic venous congestion worsens venous congestion regardless of the fluid responsiveness status, without improving perfusion parameters.

Study on the mechanism and prevention system of creep induced instability of isolated coal pillars considering time effect.

In response to the frequent occurrence of impact events in isolated coal pillars between the upper (lower) mountain areas of mining areas under conditions without obvious mining disturbance, this study takes multiple isolated coal pillar impact events that occurred in Zhaolou Coal Mine and Gengcun Coal Mine as examples. It conducts a mechanism study on the creep-induced impact ground pressure of isolated coal pillars considering the time effect. The occurrence of such impact ground pressure accidents often exhibits significant "lag" and "spontaneity". Due to the unclear mechanism of occurrence and the difficulty in grasping the unloading timing, this type of impact ground pressure has become a typical hidden disaster, posing a serious threat to the deep mining of coal mines. Based on the analysis of the creep mechanical properties of coal and rock mass, the uniaxial compression acoustic emission creep test of coal body, and the FLAC3D numerical simulation, a creep instability impact mechanical model of coal and rock mass is established. This model reveals the mechanism of creep instability impact and the stress evolution law of coal and rock mass during creep. The mechanical and energy criteria for the occurrence of impact ground pressure in isolated coal pillars under the action of unstable creep are proposed. The study shows that the action of high ground stress is a necessary condition for the occurrence of "lag-type" impact ground pressure in isolated coal pillars. Long-term unstable creep will weaken the support strength of the entry. When the elastic energy accumulated in the isolated coal pillar exceeds its ultimate bearing capacity, impact instability will occur. Based on the mechanism of occurrence of such impact accidents, targeted deep hole blasting unloading measures are proposed, providing a good reference value for the prevention and control of "lag-type" impact ground pressure accidents in isolated coal pillars.

BCL-2 and γ-H2AX immunostaining profile in urothelial bladder cancer prognosis.

Urothelial bladder carcinoma (UBC) is a malignant neoplasm of the urinary tract that is highly prevalent worldwide and has a high rate of tumor recurrence. It is known that the BCL2 apoptosis regulator (BCL-2) gene encodes a mitochondrial protein that regulates programmed death cells by apoptosis. In contrast, the H2A.X histone variant (H2AX) gene encodes a histone responsible for regulating and signaling genomic instability processes. The present study aimed to analyze the immunostaining profiles of BCL-2 and γ-H2AX proteins in tissue samples (n=80) from UBC patients (muscle-invasive MI; and non-muscle invasive NMI) using indirect immunohistochemistry and to correlate the results with prognostic and clinical parameters. BCL-2 protein expression was cytoplasmic and absent in half of the samples, including the MI and NMI groups. Strong nuclear expression was observed for γ-H2AX, predominant in the MI samples. The immunostaining profile of both proteins was not associated with tumor recurrence or invasion, and no significant associations were found in relation to prognosis (tumor grade, pathological staging). No significant correlation was found between protein profiles in malignant tissue. All in all, BCL-2 and γ-H2AX did not prove to be candidate markers for UBC clinical management in the present sample, despite their expression in malignant bladder tissue.

Patient-Reported Outcomes After Arthroscopic Superior Capsule Reconstruction With an Acellular Porcine Dermal Xenograft for Irreparable Rotator Cuff Tears.

Background: Currently, there is no consensus on the adequate management of irreparable rotator cuff tears. Arthroscopic superior capsule reconstruction (SCR) seems to be an alternative treatment option. Purpose/Hypothesis: The purpose of this study was to evaluate patient-reported outcomes up to 2 years after the treatment of irreparable rotator cuff tears with SCR using an acellular porcine dermal xenograft. It was hypothesized that SCR treatment with an acellular porcine dermal xenograft would not result in a significant clinical improvement or pain relief in patients with irreparable rotator cuff tears if the xenograft fails. Study Design: Case series; Level of evidence, 4. Methods: A total of 26 consecutive patients with irreparable rotator cuff tears were enrolled in the study between 2015 and 2019. All patients underwent SCR with acellular porcine dermal xenograft. Patient-reported outcome measures including visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the Veterans RAND 12- Item Health Survey (VR-12), and the Single Assessment Numeric Evaluation (SANE) were followed up for 2 years. For statistical analysis, the 1-way analysis of variance was used to compare means for VAS, ASES, VR-12, and SANE results between pre- and posttreatment. Magnetic resonance imaging (MRI) records were obtained at 1 year postoperatively to evaluate graft integrity. Results: In total, 22 patients were included in the patient-reported outcomes with 4 being lost at final follow-up. The mean VAS score decreased from 4.2 ± 2.5 to 1.0 ± 1.4 (P < .001) from pretreatment to 2 years postoperatively. The mean ASES - index score improved significantly from 47.7 ± 15.3 to 86.4 ± 12.9 (P < .001) and the SANE score improved from 34.0 ± 20.4 to 77.3 ± 20.2 (P < .001). In addition, a clinically important difference in the patients' quality of life was achieved, as shown by the mean changes in the VR-12 physical (+4.3) and mental scores (+9.3). Based on postoperative MRI, the dermal graft on the humeral side was intact in 15 (68.2%) patients after surgery. Conclusion: Our arthroscopic SCR with an acellular porcine dermal matrix showed significant and continuous improvement in pain and clinical scores up to a 2-year follow-up in patients with irreparable rotator cuff tears, even with structural graft failure. However, further studies and evaluation of larger patient groups are needed to evaluate the long-term effect of this procedure.

Patient-Specific Acetabular Safe Zones in Total Hip Arthroplasty: External Validation of a Quantitative Approach to Preoperatively Templating Spinopelvic Parameters.

Background: Spinopelvic mechanics are critical in total hip arthroplasty; however, there is no established consensus for adjusting acetabular component positioning based on spinopelvic parameters. This study aimed to (1) validate a recently developed Patient-Specific acetabular safe-zone calculator that factors in spinopelvic parameters and (2) compare differences with hip-spine classification targets. Methods: A total of 3750 patients underwent primary total hip arthroplasty across 3 academic referral centers, with 33 (0.88%) requiring revision for instability. Spinopelvic parameters were measured before initial total hip arthroplasty, and acetabular component position was measured following the index and revision procedures. Most operations employed either computer navigation or robotic assistance (94%). Surgical approaches included both anterior and posterior techniques. Utilizing our recently developed patient-specific safe-zone calculator, theoretical intraoperative positions were calculated and compared to true component positions before and after revision. Results: Among 33 patients who underwent revision, none dislocated at an average follow-up of 5.1 years. In the external validation cohort, the average absolute differences between the patient-specific safe-zone and the median hip-spine classification recommendation were 3.8° ± 2.1° inclination and 5.0° ± 3.2° version. For the pooled cohort, the absolute differences between the patient-specific safe-zone targets and the prerevision component positions were 7.9° ± 5.1° inclination and 11.4° ± 6.9° version. After revision, the mean absolute differences decreased to 3.6° ± 3.1° inclination and 5.8° ± 3.5° version (P < .001). Conclusions: A patient-specific approach improved acetabular component positioning accuracy within 6° of version and 4° of inclination of stable, revised hips. Patient-specific safe zones provide quantitative targets for nuanced spinopelvic preoperative planning that may mitigate risk of instability and may indicate use of assisted technologies.

DECREASED SURGICAL DURATION, LESS COMPLICATIONS, AND FASTER RETURN TO ACTIVITIES ACROSS THE LEARNING CURVE FOR THE ARTHROSCOPIC LATARJET TECHNIQUE.

OBJETIVE: This study aims to analyze the learning curves in performing the arthroscopic Latarjet surgery. METHODS: This was an observational, retrospective, single-center study. All cases of arthroscopic Latarjet performed in this institution from 2016 to 2021 were included. The data analyzed were surgical time (of the chief surgeon alone and the group of surgeons), complications, and time until the return to sports activities. Technical observations about the learning process were also reported. RESULTS: In total, 50 consecutive cases were included (93% retention of the initial sample identified at the institution). The decrease in surgical time was presented logarithmically and showed a decrease in time both for the individualized analysis of the senior surgeon (r = -0.67, p < 0.001) and for the surgical group (r = -0.476, p < 0.001). Mean operating time (and standard deviation) dropped from 235 minutes (73) in the first 10 cases to 156 minutes (34) for the subsequent cases (p < 0.001). In the first 20 cases, five intercurrences were recorded and three reoperations were performed, whereas subsequent cases presented only one intercurrence requiring surgical intervention (p = 0.032). The median time to return to sport was nine months for the first 20 cases versus six months for subsequent cases (p = 0.001). CONCLUSION: The learning curve for the arthroscopic Latarjet procedure showed a progressive decrease in operative time, complications, and time to return to sports activities. This suggests that the surgeon developed the necessary skills and confidence to reach a plateau of expertise to perform the surgical procedure. Level of evidence IV, Observational retrospective.

OBJETIVO: Analisar a curva de aprendizado para a realização artroscópica da cirurgia de Latarjet. Métodos: Este foi um estudo observacional, retrospectivo e unicêntrico. Foram incluídos todos os casos de Latarjet artroscópico realizados nesta instituição, de 2016 a 2021. Os dados analisados foram: tempo cirúrgico (somente do cirurgião chefe e do grupo de cirurgiões), complicações e tempo até o retorno às atividades esportivas. Observações técnicas sobre o processo de aprendizagem também foram relatadas. RESULTADOS: Foram incluídos 50 casos consecutivos (retenção de 93% da amostra inicial identificada na instituição). A diminuição do tempo cirúrgico foi apresentada de forma logarítmica e mostrou redução do tempo, tanto para a análise individualizada do cirurgião sênior (r = −0,67, p < 0,001) quanto para o grupo cirúrgico (r = −0,476, p < 0,001). O tempo operatório médio (e desvio padrão) caiu de 235 minutos (73) nos primeiros 10 casos para 156 minutos (34) nos casos subsequentes (p < 0,001). Nos primeiros 20 casos foram documentadas cinco intercorrências e realizadas três reoperações, enquanto nos casos subsequentes ocorreu apenas uma intercorrência com necessidade de intervenção cirúrgica (p = 0,032). O tempo médio para retorno ao esporte foi de nove meses para os primeiros 20 casos versus seis meses para os casos subsequentes (p = 0,001). Conclusão: Durante a adoção inicial do Latarjet artroscópico, houve diminuição progressiva do tempo operatório, das complicações e do tempo de retorno às atividades esportivas até que o cirurgião ganhasse a habilidade e a confiança necessárias para atingir o patamar de expertise para realização do procedimento cirúrgico. Nível de evidência IV, Retrospectivo observacional.

Accuracy and reliability of imaging modalities for studying bipolar bone loss in anterior shoulder instability: A systematic review.

PURPOSE: Recurrent shoulder instability, a common musculoskeletal disorder, often involves glenoid bone loss and Hill-Sachs lesions. However, the optimal imaging modality for accurately and reliably quantifying bipolar bone loss remains uncertain. This systematic review aims to evaluate the accuracy and reliability of various imaging modalities in assessing bipolar bone loss in anterior shoulder instability. METHODS: Major electronic databases were searched for English-language studies reporting the measurement of glenoid track width and/or determination of on/off track HSL through imaging. Studies reporting statistical measures such as area under the curve, sensitivity, specificity, positive predictive value, NPV, intraobserver reliability and interobserver reliability were included. Data extraction and risk of bias assessment were performed independently by two reviewers. RESULTS: The systematic review included 19 studies comprising 1567 shoulders. Overall, studies could be divided into those looking at the accuracy or reliability of determining glenoid track width, on- or off-track Hill-Sachs lesions and near-track lesions. Three-dimensional images of computed tomography (3D-CT) was the most reliable and accurate imaging modality to measure the glenoid track width. On the opposite, two-dimensional magnetic resonance imaging (2D-MRI) did not provide enough evidence of accuracy and reliability in the determination of On/Off track lesions and near-track lesions. CONCLUSION: 3D-CT demonstrated excellent reliability for measuring glenoid track width. However, the reliability of 2D-MRI for determining on/off track Hill-Sachs lesions is still controversial. LEVEL OF EVIDENCE: Level III.

T2WI and ADC radiomics combined with a nomogram based on clinicopathologic features to quantitatively predict microsatellite instability in colorectal cancer.

RATIONALE AND OBJECTIVES: Microsatellite instability (MSI) stratification can guide the clinical management of patients with colorectal cancer (CRC). This study aimed to establish a radiomics model for predicting the MSI status of patients with CRC before treatment. MATERIALS AND METHODS: This retrospective study was performed on 366 patients diagnosed with CRC who underwent preoperative magnetic resonance imaging (MRI) and immunohistochemical staining between February 2016 and September 2023. The participants were divided randomly into training and testing cohorts in a 7:3 ratio. The tumor volume of interest (VOI) was manually delineated on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences using 3D Slicer software, and radiomics features were extracted. Feature selection was performed using the least absolute shrinkage and selection operator method. A radiomics nomogram was developed using multiple logistic regression, and the predictive performance of the models was evaluated and compared using receiver operating characteristic curves. The calibration curve, clinical decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical application value of the model. RESULTS: The radiomics normogram combined with history of chronic enteritis, tumor location, MR-reported inflammatory response, D2-40, carcinoembryonic antigen, tumor protein 53, and monocyte was an excellent predictive tool. The area under the curve for the training and testing cohorts were 0.927 and 0.984, respectively. The DCA and CIC demonstrated favorable clinical application and net benefit. CONCLUSIONS: A radiomics nomogram based on T2WI and ADC sequences and clinicopathologic features can effectively and noninvasively predict the MSI status in CRC. This approach helps clinicians in stratifying CRC patients and making clinical decisions for personalized treatment.

Functional Outcomes of Immediate Weightbearing After Arthroscopic Lateral Ankle Ligament Repair: A Prospective Randomized Single-Center Trial.

BACKGROUND: Previous studies have revealed that early postoperative rehabilitation of chronic lateral ankle instability is just as crucial as surgical intervention. Immediate weightbearing has yielded good clinical results; however, randomized controlled studies have been limited. PURPOSE: To compare the clinical outcomes of patients with immediate weightbearing after lateral ankle ligament repair with those with delayed weightbearing after 2 weeks in a prospective randomized controlled study. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Patients who underwent arthroscopic anterior talofibular ligament repair between August 2021 and December 2022 were randomized into 2 groups-immediate weightbearing with a hard ankle brace and nonweightbearing casting for 2 weeks followed by cast removal and weightbearing. Primary outcomes were the ankle function scores as assessed using the visual analog scale at rest and during activities, the American Orthopaedic Foot & Ankle Society (AOFAS) score, and the Karlsson Ankle Functional Score (Karlsson score). Secondary outcomes were the time to return to unsupported walking, jogging, work, and exercise and change in the ankle range of motion (ROM) at 3-, 6-, and 12-month follow-ups. RESULTS: A total of 88 participants were included, consisting of 58 men and 30 women, with a mean age of 30.26 years. Computerized randomization resulted in 44 patients per group. These 2 groups displayed no difference in the AOFAS score, Karlsson score, and ankle ROM at all follow-ups. Patients who underwent immediate weightbearing had a significantly shorter time of returning to unsupported walking (P < .001). No differences were observed in the time of returning to work, jogging, and sports exercise. CONCLUSION: For patients with chronic ankle instability after arthroscopic anterior talofibular ligament repair, immediate weightbearing allowed patients to return to unsupported walking more quickly and had no negative effects on the AOFAS score, Karlsson score, times of returning to normal life, jogging, sports exercise, and ankle ROM at 3-, 6-, and 12-month follow-ups compared with cast fixation. REGISTRATION: ChiCTR2100049612 (Chinese Clinical Trial Registry; https://www.chictr.org.cn/).

Which spinal fixation technique achieves which degree of stability after thoracolumbar trauma? A systematic quantitative review.

BACKGROUND CONTEXT: Unstable traumatic spinal injuries require surgical fixation to restore biomechanical stability. PURPOSE: The purpose of this review was to summarize and quantify three-dimensional spinal stability after surgical fixation of traumatic thoracolumbar spinal injuries using different treatment strategies derived from experimental studies. STUDY DESIGN/SETTING: Systematic literature review. METHODS: Keyword-based search was performed in PubMed and Web of Science databases to identify all in vitro studies investigating stabilizing effects of different surgical fixation strategies for the treatment of traumatic spinal injuries of the thoracolumbar spine. Biomechanical stability parameters such as range of motion, neutral zone, and translation, as well as the experimental design were extracted, collected, and evaluated with respect to the type and level of injury and treatment strategy. RESULTS: A total of 66 studies with human specimens were included in this review, of which 16 studies examined the treatment of incomplete (AOSpine A3) and 34 studies the treatment of complete burst fractures (AOSpine A4). Fixations of wedge fractures (AOSpine A1, n=5 studies), ligament injuries (AOSpine B, n=7 studies), and three-column injuries (AOSpine C, n=7 studies) were investigated less frequently. Treatment approaches could be divided into five subgroups: Posterior fixation, e.g. posterior pedicle screw systems, anterior fixation, e.g. anterolateral plate fixation, combined anterior-posterior fixation, vertebral body replacement with additional instrumentation, and augmentation techniques, e.g. vertebroplasty and kyphoplasty. Minor injuries were generally treated with less invasive surgical methods such as augmentative and posterior approaches. Bisegmental posterior pedicle screw fixation led to stabilization of minor compression injuries, whereas in more severe injuries, e.g. AOSpine A4 or AOSpine C, instability remained in at least one motion plane. More invasive fixation techniques such as long segment posterior fixation, circumferential fixation, or vertebral body replacements with circumferential fixation provided total stabilization in terms of range of motion reduction even in more severe injuries. Pure augmentative treatment did not restore multidirectional stability. Neutral zone, which was reported in 25 studies, generally exhibited higher remaining increase than range of motion, which was reported in all 66 studies. Instability characteristics after treatment differed with respect to the spinal region, as thoracic injuries were more likely to remain unstable in flexion/extension, while thoracolumbar and lumbar injuries exhibited remaining instability primarily in axial rotation. CONCLUSIONS: The stabilizing effect of surgical treatment depends on the type, severity, and location of injury, as well as the fixation strategy. There is an enormous range of surgical approaches and instrumentation strategies available. Pure augmentative techniques have not been able to restore complex multidimensional stability in traumatic spinal injuries. More invasive fixation approaches such as circumferential instrumentation or vertebral body replacement constructs together with posterior or anterior-posterior fixation offer more stability even in severe spinal injuries. Future studies are required to expand the knowledge especially regarding the stabilization of minor compression injuries, ligament injuries, and rotational injuries.

Association of Homelessness and Unstable Housing With Cardiovascular Care Utilization Among Veterans.

BACKGROUND: Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization. METHODS: Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease-related specialists. Secondary outcomes included cardiovascular disease-related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest. RESULTS: Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease-related specialists (4.3% [95% CI, 2.5%-6.1%] and 14.1% [95% CI, 12.5%-15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations. CONCLUSIONS: Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed.

Round table discussion. The management of proximal scaphoid nonunion.

The management of scaphoid nonunion, although relatively common, continues to pose challenges, especially if complicated by avascular necrosis of the proximal pole, humpback or dorsal intercalated segment instability deformities, and early scaphoid nonunion advanced collapse. In this round table article, four surgeons were asked to answer key questions on a clinical example of a proximal scaphoid nonunion to outline their approach and rationale in their preferred treatment choices. The current panel of experts leans towards arthroscopic methods of treatment and most agree that arthroscopic bone grafting has become an important and revolutionary treatment option, which has yielded excellent results. However, both open and arthroscopic grafting are validated methods of treatment and which is to be performed is largely based on the surgeon's preference.

A comprehensive investigation of associations between cell death pathways and molecular and clinical features in pan-cancer.

BACKGROUND: Regulated cell death (RCD) pathways play significant roles in tumorigenesis. However, systematic investigation into correlations between RCD and various molecular and clinical features, particularly anti-tumor immunity and immunotherapy response in pan-cancer remains lacking. METHODS: Using the single-sample gene set enrichment analysis, we quantified the activities of six RCD pathways (apoptosis, autophagy, ferroptosis, cuproptosis, necroptosis, and pyroptosis) in each cancer specimen. Then, we explored associations of these six RCD pathways with tumor immunity, genomic instability, tumor phenotypes and clinical features, and responses to immunotherapy and targeted therapies in pan-cancer by statistical analyses. RESULTS: Our results showed that the RCD (except autophagy) activities were oncogenic signatures, as evidenced by their hyperactivation in late stage or metastatic cancer patients, positive correlations with tumor proliferation, stemness, genomic instability and intratumor heterogeneity, and correlation with worse survival outcomes in cancer. In contrast, autophagy was a tumor suppressive signature as its associations with molecular and clinical features in cancer shows an opposite pattern compared to the other RCD pathways. Furthermore, heightened RCD (except cuproptosis) activities were correlated with increased sensitivity to immune checkpoint inhibitors. Additionally, elevated activities of pyroptosis, autophagy, cuproptosis and necroptosis were associated with increased drug sensitivity in a broad spectrum of anti-tumor targeted therapies, while the elevated activity of ferroptosis was correlated with decreased sensitivity to numerous targeted therapies. CONCLUSION: RCD (except autophagy) activities correlate with unfavorable cancer prognosis, while the autophagy activity correlate with favorable clinical outcomes. RCD (except cuproptosis) activities are positive biomarkers for anti-tumor immunity and immunotherapy response.

Traumatic Anterior Shoulder Instability: A Systematic Review and Proposed Modern Classification System.

Numerous surgical techniques have been developed to address recurrent anterior shoulder instability, with the Bankart repair and the Latarjet procedure emerging as dominant. With recent advancements in keyhole surgery, there's been a surge in popularity for all-arthroscopic procedures. Our systematic review aims to determine if there's justification for incorporating these techniques into a classification system for guiding treatment of traumatic anterior recurrent instability. We identified and analysed a variety of key studies, including 12 systematic reviews, three prospective studies, seven non-randomized prospective and retrospective studies, along with one biomechanical study. Our study sheds light on the wide range of procedures available to shoulder surgeons dealing with traumatic anterior recurrent instability. We introduce a novel classification system (BoTH) designed to simplify the decision-making process in this context.

Concomitant osteochondral lesion of the talus in ankle instability: Utilizing clinical presentation to guide imaging decision.

Low ankle sprains are a prevalent issue, often involving the anterior talofibular ligament. While there is increased attention placed on ligamentous injuries in ankle sprains, concomitant cartilaginous injuries are frequently overlooked. This article aims to [1] evaluate the significance of magnetic resonance imaging in anterior talofibular ligament injuries to detect concurrent osteochondral lesions of the talus as well as other associated ligamentous injuries; [2] determine the importance of clinical presentation and its association with the risk of concomitant osteochondral lesions in anterior talofibular ligament injuries. We conducted a retrospective analysis of 129 patients who underwent anterior talofibular ligament reconstruction, reviewing patient data to assess the incidence of osteochondral lesions of the talus and associated ligamentous injuries. Clinical presentations were then reviewed to identify signs and symptoms associated with the occurrence of osteochondral lesions of the talus. The results indicated that calcaneofibular ligament was most injured in association with anterior talofibular ligament injuries (69.52%; n=73). Furthermore. 31.78% (n=41) of patients with anterior talofibular ligament injuries had concurrent osteochondral lesion of the talus. Analysis on clinical presentation revealed statistical significance (p<.001) between patients that had ankle joint line tenderness lasting for more than 6 weeks and the occurrence of osteochondral lesions of the talus. This study concludes that magnetic resonance imaging could be beneficial in anterior talofibular ligament injuries with patients exhibiting persistent joint line tenderness to evaluate for osteochondral lesions to ensure a comprehensive pre-operative assessment.

Exploring low- and high-order functional connectivity in chronic ankle instability through resting-state fMRI.

BACKGROUND: The functional connectivity (FC) has emerged as a valuable tool for comprehending the cerebral operational mechanism. Understanding the FC changes in patients with chronic ankle instability (CAI) helps reveal the underlying central nervous system mechanisms of the disease and provides clues for developing personalized treatment plans. OBJECTIVES: To explore differences between low- and high-order FC in patients with CAI and healthy controls, as well as the correlation among the feature connections and clinical data. METHODS: In our study, we recruited 40 patients with CAI and 42 healthy individuals who had not experienced ankle injuries. All participants underwent clinical assessments of ankle joints, collected the number of ankle sprains within the past 6 months, and performed resting-state functional magnetic resonance imaging (rs-fMRI) scans. Pearson correlation and matrix variate normal distribution (MVND) were used to construct low-order and high-order FC networks, respectively. Feature selections between groups were performed by two-sample t-tests, and a multi-kernel support vector machine (MK-SVM) was subsequently applied to combine the multiple connection patterns for the classification. Using leave-one-out cross-validation (LOOCV) to assess classification performance and identify the consensus connections contributing most to classification. RESULTS: FC was reduced in certain brain regions of CAI patients. More consensus connections were recognized in low-order FC network than in high-order FC network. The highest classification accuracy of 91.30% was achieved by combining three connection patterns. The most discriminating functional connections were primarily centered on the default mode network and spanned the visual network, sensorimotor network, ventral attention network, and central executive network. In addition, FC strength in the left cingulate and paracingulate gyrus (DCG.L) and right superior temporal gyrus (STG.R) was negatively correlated with the number of ankle sprains in the past 6 months in all FC networks (p < 0.05). CONCLUSIONS: Abnormalities in connectivity in patients with CAI were observed in both low- and high-order FC networks. The adaptive changes in the brain related to CAI may extend beyond the sensorimotor networks, primarily involving higher-level default mode networks associated with attention. Moreover, the FC strength between DCG.L and STG.R may predict the risk of ankle re-sprains and help clinicians develop personalized treatment plans.

Combined HDAC8 and checkpoint kinase inhibition induces tumor-selective synthetic lethality in preclinical models.

The elevated level of replication stress is an intrinsic characteristic of cancer cells. Targeting the mechanisms that maintain genome stability to further increase replication stress and thus induce severe genome instability has become a promising approach for cancer treatment. Here, we identify histone deacetylase 8 (HDAC8) as a drug target whose inactivation synergizes with the inhibition of checkpoint kinases to elicit substantial replication stress and compromise genome integrity selectively in cancer cells. We showed that simultaneous inhibition of HDAC8 and checkpoint kinases led to extensive replication fork collapse, irreversible cell-cycle arrest, and synergistic vulnerability in various cancer cells. The efficacy of the combination treatment was further validated in patient tumor-derived organoid (PDO) and xenograft mouse (PDX) models, providing important insights into patient-specific drug responses. Our data revealed that HDAC8 activity was essential for reducing the acetylation level of structural maintenance of chromosomes protein 3 (SMC3) ahead of replication forks and preventing R loop formation. HDAC8 inactivation resulted in slowed fork progression and checkpoint kinase activation. Our findings indicate that HDAC8 guards the integrity of the replicating genome, and the cancer-specific synthetic lethality between HDAC8 and checkpoint kinases provides a promising replication stress-targeting strategy for treating a broad range of cancers.

High prevalence of chromosome 17 in breast cancer micronuclei: a means to get rid of tumor suppressors?

Micronuclei (MN), defined as small extra-nuclear chromatin bodies enclosed by a nuclear envelope, serve as noticeable markers of chromosomal instability (CIN). The MN have been used for breast cancer (BC) screening, diagnosis, and prognosis. However, more recently they have gained attention as seats for active chromosomal rearrangements. BC subtypes exhibit differential CIN levels and aggressiveness. This study aimed to investigate MN chromosomal contents across BC subtypes, exploring its potential role in aggressiveness and pathogenesis. Immunostaining of BC cells was performed with anti-centromeric antibody followed by confocal microscopy. Further, fluorescence in situ hybridization (FISH) was done to check the presence of specific chromosomes in the MN. The real time PCR was also done from the RNA isolated from MN to check the expression of TP53 gene. BC cell lines (CLs) showed the presence of both centromere-positive ( +) and -negative ( -) MN, with significant variation in frequency among hormone and human epidermal growth factor receptor positive and triple-negative (TN) BC cells. FISH targeting chromosomes 1, 3, 8, 11, and 17 detected centromeric signals for all the above chromosomes in MN with a relatively higher prevalence of chromosome 17 in all the CLs. Out of all the CLs, TNBC cells demonstrated the highest frequency of centromere + and chromosome 17 + MN. TP53 expression could also be demonstrated inside the MN by FISH and real time PCR. Patient sample imprints also confirmed the presence of chromosome 17 in MN with polysomy of the same in corresponding nuclei. The high prevalence of chromosome 17 in BC MN may connote the importance of its rearrangements in the pathogenesis of BC. Further, the higher prevalence of chromosome 17 and 1 signals in TNBC MN point towards the significance of pathogenetic events involving the genes located in these chromosomes in evolution of this more aggressive phenotype.