Detection limitations of prion seeding activities in blood samples from patients with sporadic prion disease.

BACKGROUND: Human prion diseases (HPDs) are fatal neurodegenerative disorders characterized by abnormal prion proteins (PrPSc). However, the detection of prion seeding activity in patients with high sensitivity remains challenging. Even though real-time quaking-induced conversion (RT-QuIC) assay is suitable for detecting prion seeding activity in a variety of specimens, it shows lower accuracy when whole blood, blood plasma, and blood-contaminated tissue samples are used. In this study, we developed a novel technology for the in vitro amplification of abnormal prion proteins in HPD to the end of enabling their detection with high sensitivity known as the enhanced quaking-induced conversion (eQuIC) assay. METHODS: Three antibodies were used to develop the novel eQUIC method. Thereafter, SD50 seed activity was analyzed using brain tissue samples from patients with prion disease using the conventional RT-QUIC assay and the novel eQUIC assay. In addition, blood samples from six patients with solitary prion disease were analyzed using the novel eQuIC assay. RESULTS: The eQuIC assay, involving the use of three types of human monoclonal antibodies, showed approximately 1000-fold higher sensitivity than the original RT-QuIC assay. However, when this assay was used to analyze blood samples from six patients with sporadic human prion disease, no prion activity was detected. CONCLUSION: The detection of prion seeding activity in blood samples from patients with sporadic prion disease remains challenging. Thus, the development of alternative methods other than RT-QuIC and eQuIC will be necessary for future research.

Validation of the natural sedimentation technique in the diagnosis of chronic fasciolosis.

There are various diagnostic techniques available for chronic fasciolosis in ruminants. However, many of them exhibit low specificity and sensitivity, making them impractical for field use and in low-resource laboratories. The present study evaluates the usefulness of the Natural Sedimentation technique in diagnosing chronic fasciolosis in three domestic species conducted at the Laboratorio de Parasitología y Enfermedades Parasitarias, Facultad de Ciencias Veterinas, Universidad Nacional de Cajamarca. Fecal samples were collected from n = 323 cattle, n = 362 sheep, and n = 231 swine for Fasciola hepatica fecal egg counts. The visualization of adult parasites in animal livers post-mortem was considered the gold standard. Additionally, the sensitivity of the technique was evaluated using five different amounts of feces. In cattle, a sensitivity of 0.93 ± 0.03, specificity of 0.91 ± 0.06, positive predictive value of 0.96 ± 0.03, and negative predictive value of 0.86 ± 0.07 were obtained. In sheep, a sensitivity of 0.79 ± 0.05, specificity of 0.83 ± 0.07, positive predictive value of 0.90 ± 0.04, and negative predictive value of 0.66 ± 0.08 were observed. In swine, a sensitivity of 0.92 ± 0.06, specificity of 1.00 ± 0.00, positive predictive value of 1.00 ± 0.00, and negative predictive value of 0.96 ± 0.03 were found. There was no statistical difference in egg counts when using 1, 2, 3, 4, and 5 g of feces (p = 0.907). Furthermore, 1 to 688 fecal eggs of F. hepatica were counted in 1 g of feces. The Natural Sedimentation technique has both qualitative and quantitative applications with satisfactory results when using 1 g of feces in the diagnosis of chronic fasciolosis in domestic animals. Due to its simplicity, it can be implemented in field conditions and low-resource laboratories.

Safety of mapping the motor networks in the spinal cord using penetrating microelectrodes in Yucatan minipigs.

OBJECTIVE: The goal of this study was to assess the safety of mapping spinal cord locomotor networks using penetrating stimulation microelectrodes in Yucatan minipigs (YMPs) as a clinically translational animal model. METHODS: Eleven YMPs were trained to walk up and down a straight line. Motion capture was performed, and electromyographic (EMG) activity of hindlimb muscles was recorded during overground walking. The YMPs underwent a laminectomy and durotomy to expose the lumbar spinal cord. Using an ultrasound-guided stereotaxic frame, microelectrodes were inserted into the spinal cord in 8 animals. Pial cuts were made to prevent tissue dimpling before microelectrode insertion. Different locations within the lumbar enlargement were electrically stimulated to map the locomotor networks. The remaining 3 YMPs served as sham controls, receiving the laminectomy, durotomy, and pial cuts but not microelectrode insertion. The Porcine Thoracic Injury Behavioral Scale (PTIBS) and hindlimb reflex assessment results were recorded for 4 weeks postoperatively. Overground gait kinematics and hindlimb EMG activity were recorded again at weeks 3 and 4 postoperatively and compared with preoperative measures. The animals were euthanized at the end of week 4, and the lumbar spinal cords were extracted and preserved for immunohistochemical analysis. RESULTS: All YMPs showed transient deficits in hindlimb function postoperatively. Except for 1 YMP in the experimental group, all animals regained normal ambulation and balance (PTIBS score 10) at the end of weeks 3 and 4. One animal in the experimental group showed gait and balance deficits by week 4 (PTIBS score 4). This animal was excluded from the kinematics and EMG analyses. Overground gait kinematic measures and EMG activity showed no significant (p > 0.05) differences between preoperative and postoperative values, and between the experimental and sham groups. Less than 5% of electrode tracks were visible in the tissue analysis of the animals in the experimental group. There was no statistically significant difference in damage caused by pial cuts between the experimental and sham groups. Tissue damage due to the pial cuts was more frequently observed in immunohistochemical analyses than microelectrode tracks. CONCLUSIONS: These findings suggest that mapping spinal locomotor networks in porcine models can be performed safely, without lasting damage to the spinal cord.

Role of Genetic Testing in the Management of Indeterminate Thyroid Nodules in the Indian Setting.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.

Peritoneal fluid indocyanine green test for diagnosis of gut leakage in anastomotic leakage rats and colorectal surgery patients.

BACKGROUND: Application of indocyanine green (ICG) fluorescence has led to new developments in gastrointestinal surgery. However, little is known about the use of ICG for the diagnosis of postoperative gut leakage (GL). In addition, there is a lack of rapid and intuitive methods to definitively diagnose postoperative GL. AIM: To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery patients. METHODS: Sixteen rats were divided into two groups: GL group (n = 8) and sham group (n = 8). Approximately 0.5 mL of ICG (2.5 mg/mL) was intravenously injected postoperatively. The peritoneal fluid was collected for the fluorescence test at 24 and 48 h. Six patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG (2.5 mg/mL) on postoperative day 1. Their ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy stoma. Participants who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic test. The peritoneal fluids from drainage were collected 24 h after ICG injection. The ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging system. RESULTS: The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham group. Six samples of ostomy fluids showed green fluorescence, indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in patients. The peritoneal fluid ICG test exhibited a sensitivity of 100% and a specificity of 83.3% for the diagnosis of GL. The positive predictive value was 71.4%, while the negative predictive value was 100%. The likelihood ratios were 6.0 for a positive test result and 0 for a negative result. CONCLUSION: The postoperative ICG test in a drainage tube is a valuable and simple technique for the diagnosis of GL. Hence, it should be employed in clinical settings in patients with suspected GL.

An anatomo-functional study of the interactivity between the paracentral lobule and the primary motor cortex.

OBJECTIVE: The purpose of this study was to understand the anatomical and functional connections between the paracentral lobule (PCL) and the primary motor cortex (M1) of the human brain. METHODS: This retrospective study included 16 patients who underwent resection of lesions located near M1. Nine patients had lesions in the dominant hemisphere. Tractography was performed to visualize the connectivity between two regions of interest (ROIs)-the convexity and the interhemispheric fissure-that were shown by functional MRI to be activated during a finger tapping task. The number, mean length, and fractional anisotropy (FA) of the fibers between the ROIs were estimated. During surgery, subdural electrodes were placed on the brain surface, including the ROIs, using a navigation system. Cortico-cortical evoked potentials (CCEPs) were evoked by applying electrical stimuli to the hand region of M1 using electrodes placed on the convexity and were measured with electrodes placed on the interhemispheric fissure. To verify CCEP bidirectionality, electrical stimuli were applied to electrodes on the interhemispheric fissure that showed CCEP responses. Correlations of CCEP amplitudes and latencies with the number, mean length, and mean FA value obtained from tractography were determined. The correlations between these parameters and perioperative motor functions were also analyzed. RESULTS: Fibers of 14 patients were visualized by diffusion tensor imaging (DTI). Unidirectional CCEPs between the PCL and M1 were measurable in all 16 patients, and bidirectional CCEPs between them were measurable in 14 patients. There was no significant difference between the two directions in the maximum CCEP amplitude or latency (amplitude, p = 0.391; latency, p = 0.583). Neither the amplitude nor latency showed any apparent correlation with the number, mean length, or mean FA value of the fibers obtained from tractography. Pre- and postoperative motor function of the hands was not significantly correlated with CCEP amplitude or latency. The number and mean FA value of fibers obtained by DTI, as well as the maximum CCEP amplitude, varied between patients. CONCLUSIONS: This study demonstrated an anatomical connection and a bidirectional functional connection between the PCL, including the supplementary motor area, and M1 of the human brain. The observed variability between patients suggests possible motor function plasticity. These findings may serve as a foundation for further studies.

Epidemiology and laboratory detection of non-tuberculous mycobacteria.

The global incidence of non-tuberculous mycobacteria (NTM) infections is on the rise. This study systematically searched several databases, including PubMed, Web of Science, Google Scholar, and two Chinese libraries (Chinese National Knowledge Infrastructure and Wanfang) to identify relevant published between 2013 and 2023 related to the isolation of NTM in clinical specimens from various countries and provinces of China. Furthermore, a comprehensive literature review was conducted in PubMed and Google Scholar to identify randomized clinical trials, meta-analyses, systematic reviews, and observational studies that evaluated the diagnostic accuracy and impact of laboratory detection methods on clinical outcomes. This review presented the most recent epidemiological data and species distributions of NTM isolates in several countries and provinces of China. Moreover, it provided insights into laboratory bacteriological detection, including the identified strains, advantages and disadvantages, recent advancements, and the commercial Mycobacterium identification kits available for clinical use. This review aimed to aid healthcare workers in understanding this aspect, enhance the standards of clinical diagnosis and treatment, and enlighten them on the existing gaps and future research priorities.

Increased expression of CD70 in relapsed acute myeloid leukemia after hypomethylating agents.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, such as immunohistochemistry and flow cytometry, to investigate the expression of CD70 in bone marrow samples from treatment-naïve and relapsed AML patients after hypomethylating agents (HMA). Also, we evaluated the impact of HMA on CD70 expression and examined CD70 expression in various leukemic cell subsets and normal hematopoietic progenitors.

The effect of myelography dye on bone density measurements utilizing Hounsfield units on CT.

OBJECTIVE: Hounsfield unit (HU) measurements of bone density on CT are increasingly used for preoperative planning in spine surgery. Postmyelogram CT is another common preoperative diagnostic study. However, there is no current literature evaluating whether HU measurements on CT are affected by the presence of myelography dye. The purpose of the current study was to determine if the presence of myelography dye affects HU measurements of bone density in CT studies. METHODS: Twenty-nine preoperative spine surgery patients who underwent both standard and postmyelography CT performed within 6 months of each other were identified. HU measurements were obtained from an elliptical region of interest using the available software on a standard PACS. Measurements were obtained on the axial cut at the midvertebral body on all lumbar vertebrae on three separate occasions and an average value was calculated for comparative analysis. A 6-week gap was used between measurements of the CT scans and the CT myelograms to diminish bias. RESULTS: The mean age of the cohort was 69 years and the average BMI was 32 kg/m2. Five patients were male and 24 were female. Six of the patients had instrumentation placed prior to the initial CT scan. The average HU measurements for CT levels L1-5 were 165, 171, 145, 154, and 225, respectively, whereas HU measurements for CT myelography of levels L1-5 were 168, 177, 148, 170, and 239, respectively. Strong correlations were noted between the HU measured on CT and CT myelography for L1 (r2 = 0.951), L2 (r2 = 0.966), L4 (r2 = 0.820), and L5 (r2 = 0.900), and moderate for L3 (r2 = 0.668). CONCLUSIONS: The presence of myelography dye had no clear effect on CT HU measurements of bone density. The results of this study support the use of CT myelograms for bone density assessment in the absence of standard CT images.

Association of disruption of the right posterior arcuate fasciculus with spatial neglect.

OBJECTIVE: Spatial neglect is a debilitating condition observed in patients with right-sided brain injuries in whom there is defective awareness of the contralesional space. Although classically considered a right parietal lobe deficit, there has been increasing interest in the specific white matter (WM) architecture subserving spatial neglect. Patients who have lesions associated with chronic disruptions in visuospatial networks are of significant relevance in elucidating the WM tracts associated with spatial attention. In this study, the authors used two independent analytical methods to examine the relationship between WM connectivity changes and spatial attention. METHODS: Thirty patients with right-sided glioma underwent diffusion tensor imaging (DTI) tractography and neuropsychological testing prior to tumor resection. Spatial neglect was assessed using the Bells Test. Diffusion connectometry analysis was performed to calculate the probability of injury to 55 WM tracts. Next, quantitative DTI tractography was used to reconstruct 9 major WM tracts and obtain fractional anisotropy (FA) and streamline number values as indices of connectivity. Differences in connectivity were assessed between patients with neglect and controls. RESULTS: Of the WM tracts analyzed by diffusion connectometry, only the right posterior segment of the arcuate fasciculus (psAF) showed a higher probability of disconnection in patients with evidence of hemispatial neglect compared to tract reconstructions of previously published healthy controls (hemineglect: 42% ± 12.5%, vs control: 6.3% ± 4.8% [mean ± SEM]; p < 0.05). Of the WM tracts reconstructed by DTI tractography, only the right psAF demonstrated consistently lower indices of connectivity based on the mean streamline number (hemineglect: 550.35 ± 183.41, vs control: 1407.01 ± 319.93; p < 0.05) and FA value (hemineglect: 0.40 ± 0.013, vs control: 0.44 ± 0.0063; p < 0.05) in patients who demonstrated neglect compared to controls. The right long segment of the arcuate fasciculus, inferior frontooccipital fasciculus, and inferior longitudinal fasciculus also demonstrated a lower streamline number, but not a lower FA value, in patients with evidence of hemineglect. CONCLUSIONS: These findings suggest that parietotemporal networks mediated by the right psAF may play a critical role in visuospatial attention. This analysis may help to disentangle the organization of the visuospatial attention networks, predict deficits in patients with glioma, and optimize surgical planning.

An intraoperative accelerometry and real-time analysis tool for magnetic resonance-guided focused ultrasound thalamotomy.

Magnetic resonance-guided focused ultrasound (MRgFUS) is one of the newest surgical treatments for essential tremor (ET). During this procedure, a lesion is created within the thalamus to mitigate tremor. Targeting is done using a combination of stereotaxy, MR tractography, and sublesional heating, with tremor assessed during the procedure to gauge therapeutic effectiveness. Currently, tremor assessments are done qualitatively, but this approach requires the tremor change to be above a subjective threshold and provides no objective record of surgical tremor progression. Here, the authors present and demonstrate an MR-compatible accelerometer with custom MATLAB analysis code and graphical user interface to record, visualize, and quantify tremor in near real-time. Results can be exported and saved for future review. This method was used in 20 surgeries, with patients experiencing a 50.7% (95% CI -64.1% to -37.3%) improvement in the treated limb per the Clinical Rating Scale for Tremor. This method does not interrupt the surgery and is quantitative. As research on optimizing MRgFUS treatment for ET continues-for example, the refinement of targeting during sublesional sonications-such quantifying and recording of tremor changes will provide rapid and objective feedback.

Change in spinal bone mineral density as estimated by Hounsfield units following osteoporosis treatment with romosozumab, teriparatide, denosumab, and alendronate: an analysis of 318 patients.

OBJECTIVE: The purpose of this study was to determine the effect of osteoporosis medications on opportunistic CT-based Hounsfield units (HU). METHODS: Spine and nonspine surgery patients were retrospectively identified who had been treated with romosozumab for 3 to 12 months, teriparatide for 3 to 12 months, teriparatide for > 12 months, denosumab for > 12 months, or alendronate for > 12 months. HU were measured in the L1-4 vertebral bodies. One-way ANOVA was used to compare the mean change in HU among the five treatment regimens. RESULTS: In total, 318 patients (70% women) were included, with a mean age of 69 years and mean BMI of 27 kg/m2. There was a significant difference in mean HU improvement (p < 0.001) following treatment with romosozumab for 3 to 12 months (n = 32), teriparatide for 3 to 12 months (n = 30), teriparatide for > 12 months (n = 44), denosumab for > 12 months (n = 123), and alendronate for > 12 months (n = 100). Treatment with romosozumab for a mean of 10.5 months significantly increased the mean HU by 26%, from a baseline of 85 to 107 (p = 0.012). Patients treated with teriparatide for > 12 months (mean 23 months) experienced a mean HU improvement of 25%, from 106 to 132 (p = 0.039). Compared with the mean baseline HU, there was no significant difference after treatment with teriparatide for 3 to 12 months (110 to 119, p = 0.48), denosumab for > 12 months (105 to 107, p = 0.68), or alendronate for > 12 months (111 to 113, p = 0.80). CONCLUSIONS: Patients treated with romosozumab for a mean of 10.5 months and teriparatide for a mean of 23 months experienced improved spinal bone mineral density as estimated by CT-based opportunistic HU. Given the shorter duration of effective treatment, romosozumab may be the preferred medication for optimization of osteoporotic patients in preparation for elective spine fusion surgery.

A novel approach to evaluation of lumbar bone density using Hounsfield units in volume of interest on computed tomography imaging.

OBJECTIVE: The purpose of this retrospective study was to evaluate the relationship between bone mineral density (BMD), as assessed with dual-energy x-ray absorptiometry (DEXA), and Hounsfield units (HU) measured in volumes of interest (VOIs) and regions of interest (ROIs) on lumbar spine CT. METHODS: A retrospective analysis was performed on data of lumbar vertebrae obtained from patients who underwent both DEXA and lumbar spine CT scan within a 6-month period. Vertebrae with a history of compression fracture, infectious spondylitis, cement reinforcement, or lumbar surgery were excluded. HU measurements were performed in the VOI and ROI (midaxial, midcoronal, and midsagittal sections) with CT, whereas BMD was assessed with DEXA. Statistical analyses, including correlation assessments and receiver operating characteristic (ROC) curve analyses, were performed. RESULTS: This analysis included 712 lumbar vertebrae, with a median patient age of 72.0 years. BMD values and HU measurements in the VOI increased sequentially from L1 to L4, whereas HU values in the ROI did not show a consistent pattern. HU values in the VOI consistently showed a stronger correlation with BMD than those in the ROI. ROC analysis revealed patient-level cutoff values for the diagnosis of osteoporosis at different lumbar vertebral levels with high sensitivity and specificity, as well as an excellent area under the curve. CONCLUSIONS: This is the first study to introduce a novel approach using the HU value in the VOI to assess bone health at the lumbar spine. There is a strong correlation between the HU value in the VOI and BMD, and the HU value in the VOI can be used to predict osteoporosis.

Deep learning aided preoperative diagnosis of primary central nervous system lymphoma.

The preoperative distinction between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) can be difficult, even for experts, but is highly relevant. We aimed to develop an easy-to-use algorithm, based on a convolutional neural network (CNN) to preoperatively discern PCNSL from GBM and systematically compare its performance to experienced neurosurgeons and radiologists. To this end, a CNN-based on DenseNet169 was trained with the magnetic resonance (MR)-imaging data of 68 PCNSL and 69 GBM patients and its performance compared to six trained experts on an external test set of 10 PCNSL and 10 GBM. Our neural network predicted PCNSL with an accuracy of 80% and a negative predictive value (NPV) of 0.8, exceeding the accuracy achieved by clinicians (73%, NPV 0.77). Combining expert rating with automated diagnosis in those cases where experts dissented yielded an accuracy of 95%. Our approach has the potential to significantly augment the preoperative radiological diagnosis of PCNSL.

sCD14-ST and Related Osteoimmunological Biomarkers: A New Diagnostic Approach to Osteomyelitis.

Osteomyelitis (OM) is a major challenge in orthopedic surgery. The diagnosis of OM is based on imaging and laboratory tests, but it still presents some limitations. Therefore, a deeper comprehension of the pathogenetic mechanisms could enhance diagnostic and treatment approaches. OM pathogenesis is based on an inflammatory response to pathogen infection, leading to bone loss. The present study aims to investigate the potential diagnostic role of a panel of osteoimmunological serum biomarkers in the clinical approach to OM. The focus is on the emerging infection biomarker sCD14-ST, along with osteoimmunological and inflammatory serum biomarkers, to define a comprehensive biomarker panel for a multifaced approach to OM. The results, to our knowledge, demonstrate for the first time the diagnostic and early prognostic role of sCD14-ST in OM patients, suggesting that this biomarker could address the limitations of current laboratory tests, such as traditional inflammatory markers, in diagnosing OM. In addition, the study highlights a relevant diagnostic role of SuPAR, the chemokine CCL2, the anti-inflammatory cytokine IL-10, the Wnt inhibitors DKK-1 and Sclerostin, and the RANKL/OPG ratio. Moreover, CCL2 and SuPAR also exhibited early prognostic value.

Predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion.

OBJECTIVE: The aim of this study was to investigate the predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion (OLIF) with or without posterior internal fixation. METHODS: The authors retrospectively reviewed the records of patients who underwent OLIF between 2017 and 2022. Endplate bone quality (EBQ), mean vertebral bone quality (MVBQ), and vertebral bone quality (VBQ) scores were measured using preoperative non-contrast-enhanced T1-weighted MRI of the lumbar spine. Logistic regression analysis was used to identify factors associated with cage subsidence. Receiver operating characteristic curve analysis was used to evaluate the value of different site-specific MRI-based assessments of bone quality in predicting cage subsidence. RESULTS: Of the 124 patients who underwent OLIF, subsidence was found in 42 (33.9%). The VBQ, MVBQ, and EBQ scores were higher in the subsidence group than in the no-subsidence group. In the stand-alone OLIF (SA-OLIF) group, logistic regression analysis showed that the EBQ score was significantly associated with subsidence (OR 13.656, 95% CI 2.561-72.806; p = 0.002). Furthermore, the areas under the curve (AUCs) for using the VBQ, MVBQ, and EBQ scores and T-score to predict cage subsidence were 0.684, 0.683, 0.745, and 0.685, respectively. In the OLIF with posterior internal fixation (OLIF-PF) group, logistic regression analysis showed that the MVBQ score was significantly associated with subsidence (OR 8.301, 95% CI 2.064-33.385; p = 0.003). The AUCs for using the VBQ score, MVBQ score, and T-score to predict cage subsidence were 0.757, 0.774, and 0.685, respectively. CONCLUSIONS: There are significant differences in the predictive value of different site-specific bone quality assessments for cage subsidence among patients undergoing OLIF. For SA-OLIF, the EBQ score is recommended, while for OLIF-PF, the VBQ score is preferable.

A supervised, externally validated machine learning model for artifact and drainage detection in high-resolution intracranial pressure monitoring data.

OBJECTIVE: In neurocritical care, data from multiple biosensors are continuously measured, but only sporadically acknowledged by the attending physicians. In contrast, machine learning (ML) tools can analyze large amounts of data continuously, taking advantage of underlying information. However, the performance of such ML-based solutions is limited by different factors, for example, by patient motion, manipulation, or, as in the case of external ventricular drains (EVDs), the drainage of CSF to control intracranial pressure (ICP). The authors aimed to develop an ML-based algorithm that automatically classifies normal signals, artifacts, and drainages in high-resolution ICP monitoring data from EVDs, making the data suitable for real-time artifact removal and for future ML applications. METHODS: In their 2-center retrospective cohort study, the authors used labeled ICP data from 40 patients in the first neurocritical care unit (University Hospital Zurich) for model development. The authors created 94 descriptive features that were used to train the model. They compared histogram-based gradient boosting with extremely randomized trees after building pipelines with principal component analysis, hyperparameter optimization via grid search, and sequential feature selection. Performance was measured with nested 5-fold cross-validation and multiclass area under the receiver operating characteristic curve (AUROC). Data from 20 patients in a second, independent neurocritical care unit (Charité - Universitätsmedizin Berlin) were used for external validation with bootstrapping technique and AUROC. RESULTS: In cross-validation, the best-performing model achieved a mean AUROC of 0.945 (95% CI 0.92-0.969) on the development dataset. On the external validation dataset, the model performed with a mean AUROC of 0.928 (95% CI 0.908-0.946) in 100 bootstrapping validation cycles to classify normal signals, artifacts, and drainages. CONCLUSIONS: Here, the authors developed a well-performing supervised model with external validation that can detect normal signals, artifacts, and drainages in ICP signals from patients in neurocritical care units. For future analyses, this is a powerful tool to discard artifacts or to detect drainage events in ICP monitoring signals.

Experimental prognostic model integrating N6-methyladenosine-related programmed cell death genes in colorectal cancer.

Colorectal cancer (CRC) intricacies, involving dysregulated cellular processes and programmed cell death (PCD), are explored in the context of N6-methyladenosine (m6A) RNA modification. Utilizing the TCGA-COADREAD/CRC cohort, 854 m6A-related PCD genes are identified, forming the basis for a robust 10-gene risk model (CDRS) established through LASSO Cox regression. qPCR experiments using CRC cell lines and fresh tissues was performed for validation. The CDRS served as an independent risk factor for CRC and showed significant associations with clinical features, molecular subtypes, and overall survival in multiple datasets. Moreover, CDRS surpasses other predictors, unveiling distinct genomic profiles, pathway activations, and associations with the tumor microenvironment. Notably, CDRS exhibits predictive potential for drug sensitivity, presenting a novel paradigm for CRC risk stratification and personalized treatment avenues.

Molecular Detection of SARS-CoV-2 From Throat Swabs Performed With or Without Specimen Collection From the Tonsils: Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Testing for SARS-CoV-2 is essential to provide early COVID-19 treatment for people at high risk of severe illness and to limit the spread of infection in society. Proper upper respiratory specimen collection is the most critical step in the diagnosis of the SARS-CoV-2 virus in public settings, and throat swabs were the preferred specimens used for mass testing in many countries during the COVID-19 pandemic. However, there is still a discussion about whether throat swabs have a high enough sensitivity for SARS-CoV-2 diagnostic testing, as previous studies have reported a large variability in the sensitivity from 52% to 100%. Many previous studies exploring the diagnostic accuracy of throat swabs lack a detailed description of the sampling technique, which makes it difficult to compare the different diagnostic accuracy results. Some studies perform a throat swab by only collecting specimens from the posterior oropharyngeal wall, while others also include a swab of the palatine tonsils for SARS-CoV-2 testing. However, studies suggest that the palatine tonsils could have a tissue tropism for SARS-CoV-2 that may improve the SARS-CoV-2 detection during sampling. This may explain the variation of sensitivity reported, but no clinical studies have yet explored the differences in sensitivity and patient discomfort whether the palatine tonsils are included during the throat swab or not. OBJECTIVE: The objective of this study is to examine the sensitivity and patient discomfort of a throat swab including the palatine tonsils compared to only swabbing the posterior oropharyngeal wall in molecular testing for SARS-CoV-2. METHODS: We will conduct a randomized controlled study to compare the molecular detection rate of SARS-CoV-2 by a throat swab performed from the posterior oropharyngeal wall and the palatine tonsils (intervention group) or the posterior oropharyngeal wall only (control group). Participants will be randomized in a 1:1 ratio. All participants fill out a baseline questionnaire upon enrollment in the trial, examining their reason for being tested, symptoms, and previous tonsillectomy. A follow-up questionnaire will be sent to participants to explore the development of symptoms after testing. RESULTS: A total of 2315 participants were enrolled in this study between November 10, 2022, and December 22, 2022. The results from the follow-up questionnaire are expected to be completed at the beginning of 2024. CONCLUSIONS: This randomized clinical trial will provide us with information about whether throat swabs including specimens from the palatine tonsils will improve the diagnostic sensitivity for SARS-CoV-2 molecular detection. These results can, therefore, be used to improve future testing recommendations and provide additional information about tissue tropism for SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov NCT05611203; https://clinicaltrials.gov/study/NCT05611203. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47446.

Validación de la técnica de ganglio centinela en cáncer de cuello uterino en el Hospital de la Mujer

Introducción: el cáncer de cuello (CC) uterino representa un problema de salud pública. En Uruguay ocupa el tercer lugar en incidencia en mujeres, provocando 133 fallecimientos anuales. La afectación ganglionar es uno de sus principales factores pronósticos y condiciona el tratamiento. El ganglio centinela (GC) en estadios precoces de cáncer cervicouterino es una técnica segura que permite una adecuada estadificación y reduce la morbilidad asociada a la linfadenectomía convencional. Objetivo: validar la utilización de la técnica de la biopsia GC en estadios precoces de CC como estándar de tratamiento para la detección de metástasis ganglionares en el Hospital de la Mujer. Material y método: se realizó un estudio prospectivo, longitudinal, de casos. Se incluyó a 30 usuarias con CC en estadios iniciales, en el período comprendido entre enero de 2018 y noviembre de 2022. La marcación se realizó con tecnecio 99m (99mTc). En el mismo acto quirúrgico se realizó la linfadenectomía pélvica sistemática. Resultados: se detectó GC de forma bilateral en 29 de 30 pacientes. Con una tasa de detección por región de 98,3%. En cinco pacientes se detectaron GC metastásicos, no encontrando ganglios no centinela positivos. Una de ellas correspondió a una micrometástasis detectada por ultraestadificación. La sensibilidad fue de 100%: IC95% (56,55 -100) con VPN 100% IC95% (86,68 - 100). Conclusiones: de acuerdo con los resultados arrojados por el estudio, el equipo interdisciplinario del Hospital de la Mujer está en condiciones de utilizar la biopsia de GC de cérvix como estándar de tratamiento en el CC uterino en estadio precoz.

Introduction: Cervical cancer (CC) is a public health problem. In Uruguay, it ranks third in incidence in women, causing 133 deaths annually. Lymph node involvement is one of its main prognostic factors and determines treatment. The sentinel lymph node (SLN) in early stages of cervical cancer is a safe technique that allows for adequate staging and reduces morbidity associated with conventional lymphadenectomy. Objective: To validate the use of the SLN biopsy technique in early stages of CC as the standard treatment for detecting lymph node metastases at the Women's Hospital. Method: A prospective, longitudinal case study was conducted. Thirty patients with early-stage cervical cancer between January 2018 and November 2022 were included in the study. The marking was done with Tc99. Systematic pelvic lymphadenectomy was performed in the same surgical procedure. Results: Sentinel lymph nodes were detected bilaterally in 29 out of 30 patients. With a detection rate per region of 98.3%, metastatic SLNs were detected in 5 patients, with no positive non-sentinel nodes found. One of them corresponded to a micrometastasis detected by ultra-staging. Sensitivity was 100% (95% CI 56.55,100) with a negative predictive value of 100% (95% CI 86.68, 100). Conclusions: According to the results of the study, the interdisciplinary team at the Women's Hospital is in a position to use cervical SLN biopsy as the standard treatment for early-stage cervical cancer.

Introdução: O câncer do colo do útero (CCU) representa um problema de saúde pública. No Uruguai, ocupa o terceiro lugar em incidência em mulheres, causando 133 mortes por ano. O acometimento dos linfonodos é um dos principais fatores prognósticos e condiciona o tratamento. O linfonodo sentinela (LS) em estágios iniciais do câncer do colo do útero é uma técnica segura que permite o estadiamento adequado e reduz a morbidade associada à linfadenectomia convencional. Objetivo: Validar o uso da técnica de biópsia por LS em estágios iniciais do CCU como tratamento padrão para a detecção de metástases linfonodais no Hospital da Mulher. Materiais e métodos: Foi realizado um estudo de caso prospectivo e longitudinal. Trinta usuárias com LS em estágio inicial foram incluídas no período de janeiro de 2018 a novembro de 2022. A marcação foi realizada com Tc99. A linfadenectomia pélvica sistemática foi realizada no mesmo ato cirúrgico. Resultados: O LS foi detectado bilateralmente em 29 das 30 usuárias, com uma taxa de detecção por região de 98,3%. Em 5 pacientes foram detectados LS metastáticos e não foram encontrados nódulos não-sentinela positivos. 1 deles correspondia a uma micrometástase detectada por ultrassonografia. A sensibilidade foi de 100% CI 95% (56,55,100) com NPV 100% CI 95% (86,68, 100). Conclusões: Com base nos resultados do estudo, a equipe interdisciplinar do Hospital da Mulher está em condições de usar a biópsia de LS cervical como padrão de tratamento no câncer cervical em estágio inicial.