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External validation of yonsei nomogram predicting chronic kidney disease development after partial nephrectomy: An international, multicenter study
Objective: To externally validate Yonsei nomogram.
Methods: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis.
Results and limitation: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study.
Conclusions: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.restrictio
Guided Autotransplantation of Impacted Canines Using a CAD/CAM Surgical Template
Autotransplantation is a potential treatment alternative when orthodontic traction of an impacted tooth is difficult. In this article, we describe two cases of guided autotransplantation of an impacted canine using a computer-aided designed and manufactured surgical template. The impacted canine was segmented on preoperative cone-beam computed tomography images to ensure a sufficient periodontal ligament space and placement of the donor tooth with the least pressure on it. The canine was virtually transposed using a simulation program considering the adjacent teeth. The surgical template, which was connected to the occlusal stop on adjacent teeth, was designed and 3D-printed with polymer resin. The recipient site was prepared using the surgical template, followed by immediate transplantation of the surgically extracted canine into the socket. The transplanted donor tooth was positioned in planned infra-occlusion to prevent occlusal interference. It was then splinted with the adjacent teeth for initial stabilization. During follow-up, one transplanted tooth showed pulp canal obliteration and the other had suspected pulp necrosis; endodontic treatment was performed. One year after the procedure, the periradicular condition of both teeth was favorable. © 2023 by the authors.ope
Expression of Amine Oxidase Proteins in Adrenal Cortical Neoplasm and Pheochromocytoma
We delved into the expression of amine oxidase family proteins and their potential significance in adrenal gland neoplasm. Tissue microarrays were prepared for 132 cases of adrenal cortical neoplasm (ACN) consisting of 115 cases of adrenal cortical adenoma (ACA), 17 cases of adrenal cortical carcinoma (ACC), and 163 cases of pheochromocytoma (PCC). Immunohistochemical stainings for MAOA, MAOB, LOX, and AOC3 were performed to evaluate the H-scores and compare them with clinicopathological parameters. The H-scores of MAOA (T; p = 0.005) and MAOB (T; p = 0.006) in tumor cells (T) were high in ACN, whereas LOX (T, S; p < 0.001) in tumor and stromal cells (S) and AOC3 (T; p < 0.001) were higher in PCC. In stromal cells, MAOA (S; p < 0.001) and AOC3 (S; p = 0.010) were more expressed in ACA than in ACC. MAOB (S) in PCC showed higher H-scores when the grading of adrenal pheochromocytoma and paraganglioma (GAPP) score was 3 or higher (p = 0.027). In the univariate analysis, low MAOA expression in stromal cells of ACN was associated with shorter overall survival (p = 0.008). In conclusion, monoamine oxidase proteins revealed differences in expression between ACN and PCC and also between benign and malignant cells.ope
False Normalization of Ankle Brachial Index: A Case of Lower Extremity Peripheral Arterial Disease with Normal Ankle-Brachial Index
Screening for lower extremity peripheral arterial disease (PAD) is essential in assessing a patient’s risk of cerebrovascular disorders. The ankle-brachial index (ABI) is widely used as a screening tool for PAD, but it can produce falsely normalized results due to factors like artery calcification and collateral vessels. We report a patient with normal ABI but confirmed lower extremity PAD through ultrasound and computed tomography (CT). This case shows the limitation of ABI for PAD diagnosis. Additional tests, such as CT or ultrasound, should be considered when PAD is suspected, even if the ABI is normal.ope
Lazertinib in pretreated EGFR T790M-mutated advanced non-small cell lung cancer: A real-world multicenter study
Introduction: Lazertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that provides a high level of selectivity for sensitizing and p.Thr790Met (T790M) EGFR mutations. We aimed to collect real-world data regarding the efficacy and safety of lazertinib.
Methods: This study included patients treated with lazertinib for T790M-mutated non-small cell lung cancer who had previously been treated with an EGFR-TKI. The primary outcome measure was progression-free survival (PFS). Additionally, this study evaluated overall survival (OS), time-to-treatment failure (TTF), duration of response (DOR), objective response rate (ORR) and disease control rate (DCR). Drug safety was also assessed.
Results: In a study of 103 patients, 90 received lazertinib as a second- or third-line therapy. The ORR and DCR were 62.1% and 94.2%, respectively. The median follow-up duration was 11.1 months, and the median PFS period was 13.9 (95% confidence interval [CI], 11.0-not reached [NR]) months. OS, DOR, and TTF had not yet been determined. In a subgroup of 33 patients with evaluable brain metastases, the intracranial DCR and ORR were 93.5% and 57.6%, respectively. The median intracranial PFS period was 17.1 (95% CI, 13.9-NR) months. Approximately 17.5% of patients had dose modification or discontinuation due to adverse events, with the most common being grade 1 or 2 paresthesia.
Conclusions: The efficacy and safety of lazertinib were recapitulated in a real-world study reflecting routine clinical practice in Korea, showing durable disease control both systematically and intracranially, with manageable side effects.restrictio
Comprehensive clinical evaluation of deep learning-based auto-segmentation for radiotherapy in patients with cervical cancer
Background and purpose: Deep learning-based models have been actively investigated for various aspects of radiotherapy. However, for cervical cancer, only a few studies dealing with the auto-segmentation of organs-at-risk (OARs) and clinical target volumes (CTVs) exist. This study aimed to train a deep learning-based auto-segmentation model for OAR/CTVs for patients with cervical cancer undergoing radiotherapy and to evaluate the model's feasibility and efficacy with not only geometric indices but also comprehensive clinical evaluation.
Materials and methods: A total of 180 abdominopelvic computed tomography images were included (training set, 165; validation set, 15). Geometric indices such as the Dice similarity coefficient (DSC) and the 95% Hausdorff distance (HD) were analyzed. A Turing test was performed and physicians from other institutions were asked to delineate contours with and without using auto-segmented contours to assess inter-physician heterogeneity and contouring time.
Results: The correlation between the manual and auto-segmented contours was acceptable for the anorectum, bladder, spinal cord, cauda equina, right and left femoral heads, bowel bag, uterocervix, liver, and left and right kidneys (DSC greater than 0.80). The stomach and duodenum showed DSCs of 0.67 and 0.73, respectively. CTVs showed DSCs between 0.75 and 0.80. Turing test results were favorable for most OARs and CTVs. No auto-segmented contours had large, obvious errors. The median overall satisfaction score of the participating physicians was 7 out of 10. Auto-segmentation reduced heterogeneity and shortened contouring time by 30 min among radiation oncologists from different institutions. Most participants favored the auto-contouring system.
Conclusion: The proposed deep learning-based auto-segmentation model may be an efficient tool for patients with cervical cancer undergoing radiotherapy. Although the current model may not completely replace humans, it can serve as a useful and efficient tool in real-world clinics.ope
Neuromuscular compartmentation of the subscapularis muscle and its clinical implication for botulinum neurotoxin injection
In this study, using immunohistochemistry with fresh cadavers, deliberate histological profiling was performed to determine which fibers are predominant within each compartment. To verify the fascial compartmentation of the SSC and elucidate its histological components of type I and II fibers using macroscopic, histological observation and cadaveric simulation for providing an anatomical reference of efficient injection of the BoNT into the SSC. Seven fixed and three fresh cadavers (six males and four females; mean age, 82.5 years) were used in this study. The dissected specimens revealed a distinct fascia demarcating the SSC into the superior and inferior compartments. The Sihler's staining revealed that the upper and lower subscapular nerves (USN and LSN) innervated the SSC, with two territories distributed by each nerve, mostly corresponding to the superior and inferior compartments of the muscle, although there were some tiny communicating twigs between the USN and LSN. The immunohistochemical stain revealed the density of each type of fiber. Compared with the whole muscle area, the densities of the slow-twitch type I fibers were 22.26 ± 3.11% (mean ± SD) in the superior and 81.15 ± 0.76% in the inferior compartments, and the densities of the fast-twitch type II fiber were 77.74% ± 3.11% in the superior and 18.85 ± 0.76% in the inferior compartments. The compartments had different proportions of slow-fast muscle fibers, corresponding to the functional differences between the superior compartment as an early-onset internal rotator and the inferior compartment as a durable stabilizer of the glenohumeral joint.ope
Development and validation of an artificial intelligence model for the early classification of the aetiology of meningitis and encephalitis: a retrospective observational study
Background: Early diagnosis and appropriate treatment are essential in meningitis and encephalitis management. We aimed to implement and verify an artificial intelligence (AI) model for early aetiological determination of patients with encephalitis and meningitis, and identify important variables in the classification process.
Methods: In this retrospective observational study, patients older than 18 years old with meningitis or encephalitis at two centres in South Korea were enrolled for development (n = 283) and external validation (n = 220) of AI models, respectively. Their clinical variables within 24 h after admission were used for the multi-classification of four aetiologies including autoimmunity, bacteria, virus, and tuberculosis. The aetiology was determined based on the laboratory test results of cerebrospinal fluid conducted during hospitalization. Model performance was assessed using classification metrics, including the area under the receiver operating characteristic curve (AUROC), recall, precision, accuracy, and F1 score. Comparisons were performed between the AI model and three clinicians with varying neurology experience. Several techniques (eg, Shapley values, F score, permutation feature importance, and local interpretable model-agnostic explanations weights) were used for the explainability of the AI model.
Findings: Between January 1, 2006, and June 30, 2021, 283 patients were enrolled in the training/test dataset. An ensemble model with extreme gradient boosting and TabNet showed the best performance among the eight AI models with various settings in the external validation dataset (n = 220); accuracy, 0.8909; precision, 0.8987; recall, 0.8909; F1 score, 0.8948; AUROC, 0.9163. The AI model outperformed all clinicians who achieved a maximum F1 score of 0.7582, by demonstrating a performance of F1 score greater than 0.9264.
Interpretation: This is the first multiclass classification study for the early determination of the aetiology of meningitis and encephalitis based on the initial 24-h data using an AI model, which showed high performance metrics. Future studies can improve upon this model by securing and inputting time-series variables and setting various features about patients, and including a survival analysis for prognosis prediction.
Funding: MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea.ope
Association of non-high-density lipoprotein cholesterol trajectories with the development of non-alcoholic fatty liver disease: an epidemiological and genome-wide association study
Background: Non-alcoholic fatty liver disease (NAFLD) shares common risk factors with cardiovascular diseases. Effects of longitudinal trends in non-high-density lipoprotein (non-HDL) cholesterol on NAFLD development are not understood. This study aimed to assess the relationship between non-HDL cholesterol trajectories and the incidence of NAFLD and to identify genetic differences contributing to NAFLD development between non-HDL cholesterol trajectory groups.
Methods: We analyzed data from 2203 adults (aged 40-69 years) who participated in the Korean Genome and Epidemiology Study. During the 6-year exposure periods, participants were classified into an increasing non-HDL cholesterol trajectory group (n = 934) or a stable group (n = 1269). NAFLD was defined using a NAFLD-liver fat score > -0.640. Multiple Cox proportional hazard regression analysis estimated the hazard ratio (HR) and the 95% confidence interval (CI) for the incidence of NAFLD in the increasing group compared with the stable group.
Results: A genome-wide association study identified significant single-nucleotide polymorphisms (SNPs) associated with NAFLD. During the median 7.8-year of event accrual period, 666 (30.2%) newly developed NAFLD cases were collected. Compared with the stable non-HDL group, the adjusted HR (95% CI) for the incidence of NAFLD in the increasing non-HDL cholesterol group was 1.46 (1.25-1.71). Although there were no significant SNPs, the polygenic risk score was highest in the increasing group, followed by the stable and control groups.
Conclusion: Our study indicates that lifestyle or environmental factors have a greater effect size than genetic factors in NAFLD progression risk. Lifestyle modification could be an effective prevention strategy for NAFLD for people with elevated non-HDL cholesterol.ope